Compositions for modulating the KRAS pathway and methods of use thereof

Abstract

The present invention relates to methods for diagnosing and treating diseases associated with an increased level of Kirsten rat sarcoma viral oncogene homologue (KRAS) signaling or secreted frizzled-related protein 2 (SFRP2), as well as, compositions and methods for modulating KRAS signaling or SFRP2 for the treatment of diseases or disorders such as cancer.

Description

[0001] Attorney Docket No.206085-0150-00WO TITLE OF INVENTION COMPOSITIONS FOR MODULATING THE KRAS PATHWAY AND METHODS OF USE THEREOF CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 588,447, filed October 6, 2023, which is hereby incorporated by reference herein in its entirety. REFERENCE TO A “SEQUENCE LISTING” SUBMITTED AS AN XML FILE The present application hereby incorporates by reference the entire contents of the sequence listing xml document named “206085-0150- 00WO_Sequence_Listing.xml”. The xml file containing the sequence listing of the present application was created on September 26, 2024 and is 26,140 bytes in size. BACKGROUND OF THE INVENTION Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in the United States (R.L. Siegel et al., CA Cancer J Clin 71 (2021), 7- 33), and KRAS is mutated in 90% of patients with PDAC (B. Giri et al., Curr Opin Gastroenterol 33 (2017), 404-410). Even with improved chemotherapy regimens, the 9% five-year survival remains low (E. Oneda and A. Zaniboni, J Clin Med 8 (2019), 8(11): 1922). One of the barriers to pancreatic cancer treatment is its desmoplastic stroma. Pancreatic cancer has the highest level of stroma (~80% of its mass) of any solid organ tumor (D. Thomas and P. Radhakrishnan, Adv Exp Med Biol 1234 (2020), 57-70), which decreases the tumor vasculature and raises the interstitial pressure, shielding the tumor from chemotherapy and immune response (F. Polani et al., World J Gastroenterol 27 (2021), 2105-2121). Pancreatic stellate cells are considered the main driver of the desmoplastic reaction, promoting cancer progression (D. Thomas and P. Radhakrishnan, Mol Cancer 18 (2019), 14). In addition to pancreatic cancer, KRAS is mutated in 23% of patients with non-small cell lung cancer (NSCLC). Notably, the G12C-mutant KRAS (KRASG12C) is the most prevailing variant and closely linked to cancer development as this mutation renders KRAS persistently activated (Lee et al., 2022, Targeted oncology, 17(6), 727– 733). Secreted frizzled-related protein 2 (SFRP2) is a glycoprotein upregulated in multiple cancer types that contributes to tumor growth, migration, anti-apoptosis (A. Courtwright et al., Cancer Res (2009); M.E. Fane et al., Clin Cancer Res 26 (2020), 5709- 5719; A. Kaur et al., Nature 532 (2016), 250-4; J.L. Lee et al., Breast Cancer Res Treat 100 (2006), 49-58; M. Montagner et al., Nat Cell Biol 22 (2020), 289-296; W. Roth et al., Oncogene 19 (2000), 4210-4220; P. Techavichit et al., BMC Cancer 16 (2016), 869; S. Yamamura et al., Mol.Cancer Ther.9 (2010), 1680-1687), and angiogenesis (A. Courtwright et al., Cancer Res (2009); A. Kaur et al., Nature 532 (2016), 250-4; P. Techavichit et al., BMC Cancer 16 (2016), 869). SFRP2 upregulates markers of immune dysfunction (PD-1 and CD38) in T-cells and contributes to their exhaustion (P. Nasarre et al., Cancers (Basel) 13 (2021), 13(11), 2696). A humanized monoclonal antibody to SFRP2 (hSFRP2 mAb) that inhibits tumor growth, angiogenesis, induces tumor apoptosis (P. Nasarre et al., Cancers (Basel) 13 (2021) 13(11), 2696); D. Garcia et al., Ann Surg Oncol 26 (2019), 4782-4790), and overcomes resistance to PD-1 inhibition was previously developed (P. Nasarre et al., Cancers (Basel) 13 (2021), 13(11), 2696). It is hypothesized that SFRP2 may influence stromal growth in cancer, since it increases fibrosis in non-neoplastic pathologies (K. Kobayashi et al., Nat Cell Biol 11 (2009), 46- 55; M. Mastri et al., Am J Physiol Cell Physiol 306 (2014), C531-9). A high correlation between SFRP2 mRNA expression and stromal mRNA expression in bladder, breast, colorectal, glioblastoma, head and neck, kidney, lung, ovarian, and endometrial cancers has also been found (K.M. Vincent and L.M. Postovit, Sci Rep 7 (2017), 42719). In correlation network analyses, genes involved in EMT process and ECM structure were associated with SFRP2 expression (K.M. Vincent and L.M. Postovit, Sci Rep 7 (2017), 42719). Because of the high stromal content in pancreatic cancer, it is hypothesized that SFRP2 may play a larger role in this tumor type, not only through reducing apoptosis, increasing angiogenesis, and affecting immune cell activation, but also through activation of fibroblasts in the tumor stroma and development of a myofibroblast phenotype. Thus, there is a need in the art for more effective therapeutic strategies for pancreatic cancer and targeting SFRP2 associated stromal growth. This invention satisfies this unmet need. SUMMARY OF THE INVENTION The present invention provides KRAS signaling or SFRP2 inhibitor compositions and methods of treating or preventing a disease or disorder where a diminished level or activity of KRAS signaling or SFRP2 is desired. In some embodiments, the invention provides methods of treating or preventing a disease or disorder in a subject, the method comprising: a) detecting the level of Kirsten rat sarcoma viral oncogene homologue (KRAS) signaling in a sample; b) comparing the level of KRAS signaling to the level in a comparator control; c) diagnosing the subject as having or at risk of developing a disease or disorder when the level of KRAS signaling is increased as compared to the comparator control; and d) administering to the subject an inhibitor of SFRP2 for the treatment or prevention of the diagnosed disease or disorder. In some embodiments, the inhibitor of SFRP2 comprises an anti- SFRP2 antibody comprising a complementary determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:19, a CDR H2 comprising the amino acid sequence of SEQ ID NO:20, a CDR H3 comprising the amino acid sequence of SEQ ID NO:21, a CDR LI comprising the amino acid sequence of SEQ ID NO:22, a CDR L2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:24. In some embodiments, the comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level of KRAS signaling in a control population. In some embodiments, the disease or disorder is pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer. In some embodiments, the disease or disorder is pancreatic adenocarcinoma. In some embodiments, the disease or disorder is lung cancer. In some embodiments, the subject is human. In some embodiments, the invention provides methods of diagnosing a subject with a disease or disorder, the method comprising: a) detecting the level or activity of secreted frizzled-related protein 2 (SFRP2) in a sample, comparing the level or activity of SFRP2 to the level in a first comparator control, b) detecting the level of Kirsten rat sarcoma viral oncogene homologue (KRAS) or KRAS signaling in a sample, comparing the level of KRAS or KRAS signaling to the level in a second comparator control, and c) diagnosing the subject as having or at risk of developing a disease or disorder when the level or activity of the combination of SFRP2 and KRAS or KRAS signaling is increased as compared to the comparator control. In some embodiments, the first comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level or activity of SFRP2 in a control population, and the second comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level of KRAS or KRAS signaling in a control population. In some embodiments, the disease or disorder is pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer. In some embodiments, the disease or disorder is pancreatic adenocarcinoma. In some embodiments, the disease or disorder is lung cancer. In some embodiments, the invention provides methods of treating or preventing a disease or disorder in a subject, the method comprising the method of any one of claims 8 through 12, further comprising administering to the subject a composition for the treatment or prevention of the diagnosed disease or disorder. In some embodiments, the composition comprises an inhibitor of SFRP2, an inhibitor of KRAS signaling or a combination thereof. In some embodiments, the inhibitor comprises a chemical compound, a protein, a peptide, a peptidomimetic, an antibody, an antibody fragment, an antibody mimetic, a chimeric antibody, a bispecific antibody, a ribozyme, a small molecule chemical compound, a short hairpin RNA, RNAi, siRNA, miRNA, or a nucleic acid encoding an antisense nucleic acid molecule. In some embodiments, the method comprises administering a combination of a) Sotorasib, adagrasib or MRTX1133 and b) an anti-SFRP2 antibody. In some embodiments, the inhibitor of SFRP2 comprises an anti-SFRP2 antibody comprising a complementary determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:19, a CDR H2 comprising the amino acid sequence of SEQ ID NO:20, a CDR H3 comprising the amino acid sequence of SEQ ID NO:21, a CDR LI comprising the amino acid sequence of SEQ ID NO:22, a CDR L2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:24. In some embodiments, the method further comprises the step of administering to the subject at least one additional therapeutic or prophylactic agent. In some embodiments, the disease or disorder is at least one selected from the group consisting of pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer. In some embodiments, the disease or disorder is pancreatic adenocarcinoma. In some embodiments, the disease or disorder is lung cancer. In some embodiments, wherein the subject is human. BRIEF DESCRIPTION OF THE DRAWINGS The following detailed description of embodiments of the invention will be better understood when read in conjunction with the appended drawings. It should be understood that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings. Figure 1A through Figure 1D depict representative results of experiments demonstrating that SFRP2 mRNA expression is increased in pancreatic cancer. Figure 1A depicts representative SFRP2 mRNA levels that were compared between 32 cancer types in the TCGA database. Pancreatic cancer had the highest SFRP2 median expression levels. Figure 1B depicts the online interactive tool GEPIA that was used to compare SFRP2 mRNA levels between pancreatic cancer samples (n=179) from the RNAseq TCGA database, and normal pancreas samples (n=177) from the RNAseq GTex database. SFRP2 mRNA levels were significantly higher in pancreatic adenocarcinoma samples, compared to normal pancreas samples (*p<0.01). Figure 1C depicts the GEPIA that was used to compare disease-free survival between patients with high SFRP2 mRNA levels (n=89), and low SFRP2 RNA levels (n=36) using the Kaplan-Meier method. High SFRP2 expression was associated with significantly worse disease-free survival (hazard ratio = 2.6; p=0.0097). HR: Hazard ratio. Figure 1D depicts SFRP2 and FZD5 protein levels measured by western blot on lysates from pancreatic cancer cell lines (AsPC-1, MIA-PaCa2, and Panc02-luc) and compared to a known positive control, SVR (angiosarcoma cells), and negative controls (PBS and media). Band densities (average intensity x band surface) were normalized to the loading control to eliminate inter-sample variability to obtain the Intensity Ration. Results were normalized to the positive control, SVR. Figure 2A through Figure 2D depict representative results of experiments demonstrating that inhibition of KRAS reduces SFRP2 expression in PDAC. Figure 2A- 2D depict band densities (average intensity x band surface) normalized to the loading control, Vinculin, to eliminate inter-sample variability, to quantitatively obtain the Intensity Ratio. For each cell type, results were normalized to the untreated control: -Dox (Figure 2A), and 0h (Figure 2B). Figure 2A depicts representative western blot analysis of PDAC expressing a doxycycline (DOX)-inducible CFP-R15 monobody. DOX-induced R15 (+) reduced SRFP2 levels in both PDAC lines and a PANC-1 tumor sample. DOX: doxycycline. Figure 2B depicts representative western blot analysis of PANC-1 cells treated with DMSO or MRTX1133 (10 or 20 nM), a noncovalent selective KRASG12Dinhibitor, for various periods of time. These results show a reduction of p-ERK and SFRP2 at 4 hours compared to control. Figure 2C depicts representative results of treatment of MIA PaCa-2 cells with trametinib (MEK inhibitor) at 100 nm for 4 hours. These results show a reduction in p-ERK and SFRP2. Figure 2D depicts representative results of treatment of MIA PaCa-2 cells with buparlisib (PI3Kinase inhibitor) at 1 µM for 4 hours and show a reduction in p-AKT and SFRP2 compared to control. Figure 3A and Figure 3B depict representative results of experiments demonstrating that SFRP2 protein expression is increased in pancreatic cancer. Figure 3A depicts a blot plot of the densitometry values from a representative western blot comparing the levels of SFRP2 between tumor tissue from patients in Table 1 and their normal adjacent pancreatic tissue. Figure 3B depicts a representative western blot of tumor tissues (T) and their normal adjacent tissues (N). Densitometry was calculated by measuring the total intensity of each SFRP2 band in tumor and normal samples, and comparing them to the loading control, GAPDH. Figure 4 depicts representative results of experiments demonstrating that SFRP2 RNA expression is associated with fibrosis in pancreatic cancer. Figure 4 depicts mRNA expression of SFRP2 in pancreatic cancer patient samples from the TCGA (n=176, consisting of 95 men, 80 women, and 1 unknown). These results correlate with the ESTIMATE stromal score obtained from RNAseq data on those patients. Spearman correlation coefficient is 0.81. Figure 5A through Figure 5D depict representative results of experiments demonstrating that SFRP2 expression is associated with fibrosis in vivo. Figure 5A depicts the correlation of SFRP2 staining and degree of fibrosis in tumors from KPC mice (n=8). Figure 5B depicts representative images of staining from a KPC mouse that had high SFRP2 staining and high levels of fibrosis identified by Masson’s trichome blue staining and picrosirius red staining. Figure 5C depicts a negative control for SFRP2 immunohistochemistry staining. Figure 5D depicts representative images of staining from a KPC mouse that had low SFRP2 staining and low levels of fibrosis identified by Masson’s trichome purple staining and picrosirius yellow staining. All slides at 40X HPF: High Power Field. Scale bar: 100 µm. Figure 6A and Figure 6B depict representative results of experiments demonstrating that SFRP2 induces epithelial mesenchymal transformation and collagen production in fibroblasts. Figure 6A depicts human skin and mouse pancreatic fibroblasts that were either untreated (control) or treated for 48 hours with SFRP2 (30 nM) or TGFβ (5 nM). Protein levels were analyzed by western blot. Band densities (average intensity x band surface) were normalized to the loading control, GAPDH, to eliminate inter- sample variability. Results were normalized to the untreated control and presented as intensity ratio. Figure 6A and Figure 6B depict that TGFβ and SFRP2 treatments induce an increase of N-cadherin (A) and fibronectin (B) protein levels in both human skin and mouse pancreatic fibroblasts. Figure 7A and Figure 7B depict representative results of experiments demonstrating that SFRP2 protein expression is increased in pancreatic cancer. Additional western blots showing the levels of SFRP2 protein in tumor and matching normal adjacent tissue samples were tested to generate the results displayed in Figure 2A. GAPDH was used as a loading control. Figure 8 depicts representative results of experiments demonstrating that SFRP2 is regulated by KRAS in lung cancer cells. Western blot of NCI-H358 KRAS12CLung Cancer Cells treated with KRAS inhibitor ARS 16201µM or PBS for 6 hours. Cells were lysed and subjected to Western blot. There is a decrease in phosphor-ERK (positive control) in ARS 1620 treated cells. There is also a decrease in SFRP2 at 6 hours in ARS 1620 treated cells, indicating that SFRP2 is regulated by KRAS in lung cancer cells. DETAILED DESCRIPTION The present invention provides KRAS signaling or SFRP2 inhibitor compositions and methods of treating or preventing a disease or disorder where a diminished level or activity of KRAS signaling or SFRP2 is desired. In some embodiments, the present invention provides compositions and methods for diminishing KRAS activity or KRAS signaling, for example, diminishing the activity of KRAS downstream targets such as the ERK-MAPK pathway and the PI3Kinase pathway. In some embodiments, the present invention provides compositions and methods for diminishing SFRP2 level or activity. Definitions Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. As used herein, each of the following terms has the meaning associated with it in this section. The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. “About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods. The term “antibody” means an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing (e.g., a glycoprotein), through at least one antigen recognition site within the variable region of the immunoglobulin molecule. As used herein, the term “antibody” encompasses polyclonal antibodies, monoclonal antibodies, chimeric antibodies, humanized antibodies, human antibodies, and any other immunoglobulin molecule so long as the antibodies exhibit the desired biological activity. An antibody can be of any the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses (isotypes) thereof (e.g. IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2), based on the identity of their heavy-chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively. The different classes of immunoglobulins have different and well known subunit structures and three- dimensional configurations. Antibodies can be naked, part of a fusion protein, or conjugated to other molecules such as toxins, radioisotopes, etc. The term “antibody fragment” refers to a portion of an antibody. An “antigen-binding fragment,” “antigen-binding domain,” or “antigen-binding region,” refers to a portion of an antibody that binds to an antigen. An antigen-binding fragment can contain the antigenic determining regions of an antibody (e.g., the complementarity determining regions (CDR)). An antigen-binding fragment can contain some or all of the VH and / or VL chain polypeptides of an antibody. Examples of antigen-binding fragments of antibodies include, but are not limited to Fab, Fab′, F(ab′)2, and Fv fragments, linear antibodies, and single chain antibodies. An antigen-binding fragment of an antibody can be derived from any animal species, such as rodents (e.g., mouse, rat, or hamster) and humans or can be artificially produced. The terms “anti-SFRP2 antibody,” “SFRP2 antibody” and “antibody that binds to SFRP2” refer to an antibody that is capable of binding SFRP2 with sufficient affinity such that the antibody is useful as a diagnostic, a therapeutic, and / or as a modulator of SFRP2 activity. A antibody that is “blocking” or that “blocks” or that is “inhibitory” or that “inhibits” is an antibody that reduces or inhibits (partially or completely) binding of its target protein to one or more ligands when the antibody is bound to the target protein, and / or that reduces or inhibits (partially or completely) one or more activities or functions of the target protein when the antibody is bound to the target protein. The term “anti-tumor effect” as used herein, refers to a biological effect which can be manifested by various means, including but not limited to, e.g., a decrease in tumor volume, a decrease in the number of tumor cells, a decrease in the number of metastases, an increase in life expectancy, decrease in tumor cell proliferation, decrease in tumor cell survival, or amelioration of various physiological symptoms associated with the cancerous condition. An “anti-tumor effect” can also be manifested by the ability of the peptides, polynucleotides, cells and antibodies of the invention in prevention of the occurrence of tumor in the first place. The term “humanized” antibody or antigen-binding fragment thereof refers to forms of non-human (e.g. murine) antibodies or antigen-binding fragments that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences. Typically, humanized antibodies or antigen-binding fragments thereof are human immunoglobulins in which residues from the complementarity determining regions (CDRs) are replaced by residues from the CDRs of a non-human species (e.g. mouse, rat, rabbit, hamster) that have the desired specificity, affinity, and capability (“CDR grafted”) (Jones et al., Nature 321:522- 525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239:1534-1536 (1988)). The humanized antibody or antigen-binding fragment thereof can be further modified by the substitution of additional residues either in the Fv framework region and / or within the replaced non-human residues to refine and optimize the specificity, affinity, and / or capability of the antibody or antigen-binding fragment thereof. In general, the humanized antibody or antigen-binding fragment thereof will comprise VH and VL that comprise substantially all of at least one, and typically two or three, of the CDR regions that correspond to the non-human immunoglobulin, whereas all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody or antigen-binding fragment thereof can also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are described in U.S. Pat. No.5,225,539; Roguska et al., Proc. Natl. Acad. Sci., USA, 91 (3):969-973 (1994), and Roguska et al., Protein Eng.9 (10):895-904 (1996). In some aspects, a “humanized antibody” is a resurfaced antibody. “Immunotherapy” refers to any medical intervention that induces, suppresses or enhances the immune system of a patient for the treatment of a disease. In some embodiments, immunotherapies activate a patient’s innate and / or adaptive immune responses (e.g. T cells) to more effectively target and remove a pathogen or cure a disease, such as cancer or an immune disease. “Effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological result. Such results may include, but are not limited to, the inhibition of virus infection as determined by any means suitable in the art. As used herein “endogenous” refers to any material from or produced inside an organism, cell, tissue or system. As used herein, the term “exogenous” refers to any material introduced from or produced outside an organism, cell, tissue or system. The term “expression” as used herein is defined as the transcription and / or translation of a particular nucleotide sequence driven by its regulatory sequences. “Parenteral” administration of an immunogenic composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques. The term “nucleic acid” or “polynucleotide” refers to deoxyribonucleic acids (DNA) or ribonucleic acids (RNA) and polymers thereof in either single- or double- stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs, SNPs, and complementary sequences as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and / or deoxyinosine residues (Batzer et al., Nucleic Acid Res.19:5081 (1991); Ohtsuka et al., J. Biol. Chem.260:2605-2608 (1985); and Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)). As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein’s or peptide’s sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof. The term “promoter” as used herein is defined as a DNA sequence recognized by the synthetic machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence. As used herein, the term “promoter / regulatory sequence” means a nucleic acid sequence which is required for expression of a gene product operably linked to the promoter / regulatory sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements which are required for expression of the gene product. The promoter / regulatory sequence may, for example, be one which expresses the gene product in a tissue specific manner. As used herein, the term “pharmaceutical formulation” refers to a preparation which is in such form as to permit the biological activity of the active ingredient to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. The formulation can be sterile. As used herein the language “pharmaceutically acceptable carrier” is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions. As used herein, the term “SFRP2” refers to secreted-frizzled related protein 2 polypeptides including, but not limited to, native SFRP2 polypeptides and any naturally occurring variants thereof. As used herein, the term “human SFRP2” refers to a polypeptide comprising the amino acid sequence of: MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPVNLQLCHGIEY QNMRLPNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLD ETIQPCHSLCVQVKDRCAPVMSAFGFPWPDMLECDRFPQDNDLCIPLASSDHLLP ATEEAPKVCEACKNKNDDDNDIMETLCKNDFALKIKVKEITYINRDTKIILETKSK TIYKLNGVSERDLKKSVLWLKDSLQCTCEEMNDINAPYLVMGQKQGGELVITSV KRWQKGQREFKRISRSIRKLQC (SEQ ID NO: 12). An “SFRP2 polynucleotide,” “SFRP2 nucleotide,” or “SFRP2 nucleic acid” refers to a polynucleotide encoding any SFRP2, including those described above. As used herein, the terms “subject” and “patient” are used interchangeably. The subject can be a mammal such as a non-human animal (e.g., cow, pig, horse, cat, dog, rat, mouse, monkey or other primate, etc.). In some aspects, the subject is a human. The term “therapeutic” as used herein means a treatment. A therapeutic effect is obtained by reduction, suppression, remission, or eradication of a disease state. The term “prophylaxis” as used herein means the prevention of or protective treatment for a disease or disease state. By the term “specifically binds,” as used herein, is meant an antibody or antigen binding fragment thereof, or a ligand, which recognizes and binds with a cognate binding partner present in a sample, but which antibody, antigen binding fragment thereof or ligand does not substantially recognize or bind other molecules in the sample. As used herein, the terms “variable region” or “variable domain” are used interchangeably and are common in the art. The variable region typically refers to a portion of an antibody, generally, a portion of a light or heavy chain, typically about the amino-terminal 110 to 120 amino acids or 110 to 125 amino acids in the mature heavy chain and about 90 to 115 amino acids in the mature light chain, which differ extensively in sequence among antibodies and are used in the binding and specificity of a particular antibody for its particular antigen. The terms “VL” and “VL domain” are used interchangeably to refer to the light chain variable region of an antibody. The terms “VH” and “VH domain” are used interchangeably to refer to the heavy chain variable region of an antibody. The “hypervariable regions” in each chain are held together in close proximity by FRs, and with the hypervariable regions from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al, Sequences of Proteins of Immunological Interest, 1992; Chothia et al., Conformations of immunoglobulin hypervariable regions. Nature (1989) 342:877-83.). The term “hypervariable region” as used herein refers to the amino acid residues of an antibody, which are responsible for antigen binding. The hypervariable region generally comprises amino acid residues from a “complementary determining region” or “CDR”, the latter being of highest sequence variability and / or involved in antigen recognition. Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. Therapeutic Inhibitor Compositions and Methods of Use In various embodiments, the present invention includes KRAS signaling or SFRP2 inhibitor compositions and methods of treating or preventing a disease or disorder where a diminished level or activity of KRAS signaling or SFRP2 is desired. One non-limiting example of a disease or disorder where a diminished level or activity of KRAS signaling or SFRP2 is desired which can be treated or prevented with the compositions and methods of the invention includes cancer. In various embodiments, the KRAS signaling or SFRP2 inhibitor compositions and methods of treatment or prevention of the invention diminish the amount of KRAS signaling or SFRP2 polypeptide, the amount of KRAS or SFRP2 protein, the amount of KRAS or SFRP2 mRNA, the amount of KRAS or SFRP2 enzymatic activity, the amount of enzymatic activity of KRAS downstream targets, or a combination thereof. It will be understood by one skilled in the art, based upon the disclosure provided herein, that a decrease in the level of KRAS or SFRP2 encompasses the decrease in KRAS or SFRP2 expression, including transcription, translation, or both, and also encompasses promoting the degradation of KRAS or SFRP2, including at the RNA level (e.g., RNAi, shRNA, etc.) and at the protein level (e.g., Ubiquitination, etc.) The skilled artisan will also appreciate, once armed with the teachings of the present invention, that a decrease in the level of KRAS or SFRP2 includes a decrease in a KRAS or SFRP2 activity (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.). Thus, decreasing the level or activity of KRAS or SFRP2 includes, but is not limited to, decreasing transcription, translation, or both, of a nucleic acid encoding KRAS or SFRP2; and it also includes decreasing any activity of a SFRP2 polypeptide, or peptide fragment thereof, as well. The KRAS or SFRP2 inhibitor compositions and methods of the invention can selectively inhibit KRAS or SFRP2, or can inhibit both KRAS or SFRP2 and one or more additional molecule. Inhibition of KRAS or SFRP2 can be assessed using a wide variety of methods, including those disclosed herein, as well as methods known in the art or to be developed in the future. That is, the routineer would appreciate, based upon the disclosure provided herein, that decreasing the level or activity of KRAS or SFRP2 can be readily assessed using methods that assess the level of a nucleic acid encoding KRAS or SFRP2 (e.g., mRNA), the level of a KRAS or SFRP2 polypeptide, or peptide fragment thereof, present in a biological sample, the level of KRAS or SFRP2 activity (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.), or combinations thereof. Inhibition of KRAS signaling or SFRP2 can be assessed using a wide variety of methods, including those disclosed herein, as well as methods known in the art or to be developed in the future. That is, the routineer would appreciate, based upon the disclosure provided herein, that decreasing the level or activity of KRAS or SFRP2 can be readily assessed using methods that assess the level of a nucleic acid encoding KRAS or SFRP2 (e.g., mRNA), the level of a KRAS or SFRP2 polypeptide, or peptide fragment thereof, present in a biological sample, the level of KRAS or SFRP2 activity (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.), or combinations thereof. One skilled in the art, based upon the disclosure provided herein, would understand that the invention is useful in treating or preventing in a subject in need thereof, whether or not the subject is also being treated with other medication or therapy. Further, the skilled artisan would further appreciate, based upon the teachings provided herein, that the disease or disorders treatable by the compositions and methods described herein encompass any disease or disorder where KRAS signaling or SFRP2 plays a role and where diminished KRAS signaling or SFRP2 level or activity will promote a positive therapeutic outcome. In various embodiments, the disease or disorder treatable or preventable using the compounds and methods of the invention include, but are not limited to, pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer. In some embodiments, the pancreatic cancer is pancreatic adenocarcinoma. In some embodiments, the disease or disorder is lung cancer. In another embodiment, the KRAS signaling or SFRP2 inhibitor of the invention can be administered to a patient who is being treated with exogenous KRAS or SFRP2, recombinant KRAS or SFRP2, and / or a KRAS or SFRP2 activator, in order to control, titrate, diminish, or stabilize the level or activity of endogenous and / or exogenous KRAS or SFRP2 in the patient. The KRAS or SFRP2 inhibitor compositions and methods of the invention that decrease the level or activity (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.) of KRAS or SFRP2, include, but should not be construed as being limited to, a chemical compound, a protein, a peptide, a peptidomimetic, an antibody, an antibody fragment, an antibody mimetic, a ribozyme, a small molecule chemical compound, an short hairpin RNA, RNAi, an antisense nucleic acid molecule (e.g., siRNA, miRNA, etc.), a nucleic acid encoding an antisense nucleic acid molecule, a nucleic acid sequence encoding a protein, a KRAS or SFRP2 receptor, or combinations thereof. In some embodiments, the inhibitor is an allosteric inhibitor. One of skill in the art would readily appreciate, based on the disclosure provided herein, that a KRAS or SFRP2 inhibitor composition encompasses any chemical compound that decreases the level or activity of KRAS or SFRP2. Additionally, a KRAS or SFRP2 inhibitor composition encompasses a chemically modified compound, and derivatives, as is well known to one of skill in the chemical arts. The KRAS or SFRP2 inhibitor compositions and methods of the invention that decrease the level or activity (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.) of KRAS or SFRP2 include antibodies, and fragments thereof. The antibodies of the invention include a variety of forms of antibodies including, for example, polyclonal antibodies, monoclonal antibodies, intracellular antibodies (“intrabodies”), Fv, Fab and F(ab)2, single chain antibodies (scFv), heavy chain antibodies (such as camelid antibodies), synthetic antibodies, chimeric antibodies, and humanized antibodies. In some embodiments, the antibody of the invention is an antibody that specifically binds to KRAS or SFRP2. Further, one of skill in the art, when equipped with this disclosure and the methods exemplified herein, would appreciate that a KRAS or SFRP2 inhibitor composition includes such inhibitors as discovered in the future, as can be identified by well-known criteria in the art of pharmacology, such as the physiological results of inhibition of KRAS or SFRP2 as described in detail herein and / or as known in the art. Therefore, the present invention is not limited in any way to any particular KRAS or SFRP2 inhibitor composition as exemplified or disclosed herein; rather, the invention encompasses those inhibitor compositions that would be understood by the routineer to be useful as are known in the art and as are discovered in the future. Further methods of identifying and producing KRAS or SFRP2 inhibitor compositions are well known to those of ordinary skill in the art, including, but not limited to, obtaining an inhibitor from a naturally occurring source. Alternatively, a KRAS or SFRP2 inhibitor can be synthesized chemically. Further, the person of skill in the art would appreciate, based upon the teachings provided herein, that a KRAS or SFRP2 inhibitor composition can be obtained from a recombinant organism. Compositions and methods for chemically synthesizing KRAS or SFRP2 inhibitors and for obtaining them from natural sources are well known in the art and are described in the art. One of skill in the art will appreciate that an inhibitor can be administered as a chemical compound, a protein, a peptide, a peptidomimetic, an antibody, an antibody fragment, an antibody mimetic, a ribozyme, a small molecule chemical compound, a short hairpin RNA, RNAi, an antisense nucleic acid molecule (e.g., siRNA, miRNA, etc.), a nucleic acid encoding an antisense nucleic acid molecule, a nucleic acid sequence encoding a protein, or a combination thereof. Numerous vectors and other compositions and methods are well known for administering a protein or a nucleic acid construct encoding a protein to cells or tissues. Therefore, the invention includes a method of administering a protein or a nucleic acid encoding a protein that is an inhibitor of KRAS or SFRP2. One of skill in the art will realize that diminishing the amount or activity of a molecule that itself increases the level or activity of KRAS or SFRP2 can serve in the compositions and methods of the present invention to decrease the level or activity of KRAS or SFRP2. Antisense oligonucleotides are DNA or RNA molecules that are complementary to some portion of an RNA molecule. When present in a cell, antisense oligonucleotides hybridize to an existing RNA molecule and inhibit translation into a gene product. Inhibiting the expression of a gene using an antisense oligonucleotide is well known in the art (Marcus-Sekura, 1988, Anal. Biochem.172:289), as are methods of expressing an antisense oligonucleotide in a cell (Inoue, U.S. Pat. No.5,190,931). The methods of the invention include the use of an antisense oligonucleotide to diminish the amount of KRAS or SFRP2, or to diminish the amount of a molecule that causes an increase in the amount or activity of KRAS or SFRP2, thereby decreasing the amount or activity of KRAS or SFRP2. Contemplated in the present invention are antisense oligonucleotides that are synthesized and provided to the cell by way of methods well known to those of ordinary skill in the art. As an example, an antisense oligonucleotide can be synthesized to be between about 10 and about 100, more preferably between about 15 and about 50 nucleotides long. The synthesis of nucleic acid molecules is well known in the art, as is the synthesis of modified antisense oligonucleotides to improve biological activity in comparison to unmodified antisense oligonucleotides (Tullis, 1991, U.S. Pat. No. 5,023,243). Similarly, the expression of a gene may be inhibited by the hybridization of an antisense molecule to a promoter or other regulatory element of a gene, thereby affecting the transcription of the gene. Methods for the identification of a promoter or other regulatory element that interacts with a gene of interest are well known in the art, and include such methods as the yeast two hybrid system (Bartel and Fields, eds., In: The Yeast Two Hybrid System, Oxford University Press, Cary, N.C.). Alternatively, inhibition of a gene expressing KRAS or SFRP2, or of a gene expressing a protein that increases the level or activity of KRAS or SFRP2, can be accomplished through the use of a ribozyme. Using ribozymes for inhibiting gene expression is well known to those of skill in the art (see, e.g., Cech et al., 1992, J. Biol. Chem.267:17479; Hampel et al., 1989, Biochemistry 28: 4929; Altman et al., U.S. Pat. No.5,168,053). Ribozymes are catalytic RNA molecules with the ability to cleave other single-stranded RNA molecules. Ribozymes are known to be sequence specific, and can therefore be modified to recognize a specific nucleotide sequence (Cech, 1988, J. Amer. Med. Assn.260:3030), allowing the selective cleavage of specific mRNA molecules. Given the nucleotide sequence of the molecule, one of ordinary skill in the art could synthesize an antisense oligonucleotide or ribozyme without undue experimentation, provided with the disclosure and references incorporated herein. Alternatively, inhibition of a gene expressing KRAS or SFRP2, or of a gene expressing a protein that increases the level or activity of KRAS or SFRP2, can be accomplished through the use of a short hairpin RNA or antisense RNA, including siRNA, miRNA, and RNAi. Given the nucleotide sequence of the molecule, one of ordinary skill in the art could synthesize a short hairpin RNA or antisense RNA without undue experimentation, provided with the disclosure and references incorporated herein. One of skill in the art will appreciate that inhibitors of KRAS or SFRP2 can be administered acutely (e.g., over a short period of time, such as a day, a week or a month) or chronically (e.g., over a long period of time, such as several months or a year or more). One of skill in the art will appreciate that inhibitors of KRAS or SFRP2 can be administered singly or in any combination with other agents. Further, KRAS or SFRP2 inhibitors can be administered singly or in any combination in a temporal sense, in that they may be administered concurrently, or before, and / or after each other. One of ordinary skill in the art will appreciate, based on the disclosure provided herein, that KRAS or SFRP2 inhibitor compositions can be used to treat or prevent a disease or disorder in a subject in need thereof, and that an inhibitor composition can be used alone or in any combination with another inhibitor to effect a therapeutic result. In various embodiments, any of the inhibitors of KRAS or SFRP2 of the invention described herein can be administered alone or in combination with other inhibitors of other molecules associated with cancer. It will be appreciated by one of skill in the art, when armed with the present disclosure including the methods detailed herein, that the invention is not limited to treatment of a disease or disorder, such as cancer, that is already established. Particularly, the disease or disorder need not have manifested to the point of detriment to the subject; indeed, the disease or disorder need not be detected in a subject before treatment is administered. That is, significant disease or disorder does not have to occur before the present invention may provide benefit. Therefore, the present invention includes a method for preventing a disease or disorder in a subject, in that a KRAS or SFRP2 inhibitor composition, as discussed previously elsewhere herein, can be administered to a subject prior to the onset of the disease or disorder, thereby preventing the disease or disorder from developing. The preventive methods described herein also include the treatment of a subject that is in remission for the prevention of a recurrence of a disease or disorder. One of skill in the art, when armed with the disclosure herein, would appreciate that the prevention of a disease or disorder encompasses administering to a subject a KRAS or SFRP2 inhibitor composition as a preventative measure against the disease or disorder, including cancer. As more fully discussed elsewhere herein, methods of decreasing the level or activity of KRAS signaling or SFRP2 encompass a wide plethora of techniques for decreasing not only KRAS signaling or SFRP2 activity, but also for decreasing expression of a nucleic acid encoding KRAS or SFRP2, including either a decrease in transcription, a decrease in translation, or both. Additionally, as disclosed elsewhere herein, one skilled in the art would understand, once armed with the teaching provided herein, that the present invention encompasses a method of preventing a wide variety of diseases, disorders and pathologies where a decrease in expression and / or activity of KRAS or SFRP2 mediates, treats or prevents the disease, disorder or pathology. Methods for assessing whether a disease relates to the levels or activity of KRAS signaling or SFRP2 are known in the art. Further, the invention encompasses treatment or prevention of such diseases discovered in the future. The invention encompasses administration of an inhibitor of KRAS signaling or SFRP2 to practice the methods of the invention; the skilled artisan would understand, based on the disclosure provided herein, how to formulate and administer the appropriate KRAS or SFRP2 inhibitor to a subject. However, the present invention is not limited to any particular method of administration or treatment regimen. The invention provides compositions that bind to KRAS or SFRP2. In some embodiments, the KRAS or SFRP2 binding agent inhibits KRAS or SFRP2 levels or activity. Thus, in diseases and conditions where a reduction of KRAS signaling or SFRP2 activity would be beneficial, such inhibitory KRAS or SFRP2 binding agents can potentially act as therapeutics. In some instances, in addition to its potential therapeutic role, KRAS signaling or SFRP2 can be used as a diagnostic marker for diseases or disorders including, but not limited, to cancer. Accordingly, also included in the invention are methods of diagnosing susceptibility to disorders and diseases, including cancer, based on the detection and / or quantitation of KRAS signaling or SFRP2. For example, disorders and diseases such as pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer, can all be diagnosed, evaluated and monitored by determining KRAS signaling and / or SFRP2 levels. In some embodiments, evaluating or monitoring pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer include detecting the level of KRAS signaling or SFRP2 prior to and again following administration of a therapeutic agent. The KRAS or SFRP2 inhibitor compositions of the invention that decrease the level or activity (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.) of KRAS or SFRP2 include, but should not be construed as being limited to, a chemical compound, a protein, a peptide, a peptidomimetic, an antibody, an antibody fragment, an antibody mimetic, a ribozyme, a small molecule chemical compound, an short hairpin RNA, RNAi, an antisense nucleic acid molecule (e.g., siRNA, miRNA, etc.), a nucleic acid encoding an antisense nucleic acid molecule, a nucleic acid sequence encoding a protein, a competitive inhibitor, or combinations thereof. In some embodiments, the inhibitor is an allosteric inhibitor. One of skill in the art would readily appreciate, based on the disclosure provided herein, that a KRAS or SFRP2 inhibitor composition encompasses a chemical compound that decreases the level or activity of KRAS or SFRP2. Additionally, a KRAS or SFRP2 inhibitor composition encompasses a chemically modified compound, and derivatives, as is well known to one of skill in the chemical arts. The KRAS or SFRP2 inhibitor compositions of the invention that decrease the level or activity (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.) of KRAS or SFRP2 include antibodies, and fragments thereof. The antibodies of the invention include a variety of forms of antibodies including, for example, polyclonal antibodies, monoclonal antibodies, intracellular antibodies (“intrabodies”), Fv, Fab and F(ab)2, single chain antibodies (scFv), heavy chain antibodies (such as camelid antibodies), synthetic antibodies, chimeric antibodies, and a humanized antibodies. In some embodiments, the antibody of the invention is an antibody that specifically binds to KRAS or SFRP2. In some embodiments, the antibodies of the invention are bispecific antibodies, where the first specificity is to KRAS and the second specificity is to SFRP2. In some embodiments, the antibodies of the invention are bispecific antibodies, where the first specificity is to KRAS or SFRP2 and the second specificity is to a second binding partner molecule that is carried and deployed to an anatomic location where KRAS or SFRP2 binding is desired. Antibodies, including KRAS or SFRP2 binding fragments thereof, of the present invention include, in certain embodiments, antibody amino acid sequences encoded by any suitable polynucleotide, or any isolated or formulated antibody. Further, antibodies of the present disclosure comprise antibodies having the structural and / or functional features of KRAS or SFRP2 binding. In some embodiments, the anti-KRAS or anti-SFRP2 antibody binds KRAS or SFRP2 and, thereby partially or substantially alters at least one biological activity of KRAS or SFRP2 (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.). In some embodiments, anti-KRAS or anti-SFRP2 antibodies of the invention immunospecifically bind at least one specified epitope specific to KRAS or SFRP2, and do not specifically bind to other polypeptides, other than KRAS or SFRP2. The at least one epitope can comprise at least one antibody binding region that comprises at least one portion of the KRAS or SFRP2 protein. The term “epitope” as used herein refers to a protein determinant capable of binding to an antibody. Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents. The binding portion of an antibody comprises one or more fragments of an antibody that retain the ability to specifically bind to binding partner molecule (e.g., KRAS or SFRP2). It has been shown that the binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments encompassed within the term “binding portion” of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR). Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (scFv); see e.g., Bird et al. (1988) Science 242:423- 426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). Such single chain antibodies are also intended to be encompassed within the term “binding portion” of an antibody. These antibody fragments are obtained using conventional techniques known to those with skill in the art, and the fragments are screened for utility in the same manner as are intact antibodies. Binding portions can be produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact immunoglobulins. An antibody that binds to KRAS or SFRP2 of the invention is an antibody that inhibits, blocks, or interferes with at least one KRAS or SFRP2 activity (e.g., enzymatic activity, substrate binding activity, receptor binding activity, etc.), in vitro, in situ and / or in vivo. A suitable anti-KRAS or anti-SFRP2 antibody, specified portion, or variant can also optionally affect at least one KRAS or SFRP2 activity or function, such as but not limited to, RNA, DNA or protein synthesis, protein release, and / or KRAS signaling. In some embodiments, the anti-SFRP2 antibody comprises a humanized anti-secreted frizzled-related protein 2 (SFRP2) antibody or antigen binding fragment thereof which binds SFRP2, wherein said antibody or antigen binding fragment thereof comprises a complementary determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:19, a CDR H2 comprising the amino acid sequence of SEQ ID NO:20, a CDR H3 comprising the amino acid sequence of SEQ ID NO:21, a CDR L1 comprising the amino acid sequence of SEQ ID NO:22, a CDR L2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:24. In some embodiments, the anti-SFRP2 antibody comprises a humanized anti-secreted frizzled-related protein 2 (SFRP2) antibody or antigen binding fragment thereof which binds SFRP2, wherein said antibody or antigen binding fragment thereof comprises a variable heavy (VH) chain polypeptide at least 90%, 95%, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, 2, 3, or 4; and further wherein said antibody or antigen binding fragment thereof comprises a variable light (VL) chain polypeptide at least 90%, 95%, or 99% identical to a polypeptide comprising the amino acid sequence of SEQ ID NO: 5, 6, 7, 8, or 9. Table 1: COMPLEMENTARY DETERMINING REGION AMINO ACID SEQUENCES SEQ ID NO DESCRIPTION SEQUENCE 19 CDRH1 RYWWH 20CDRH2 RIDPNSGTTRFIEKFKT21 CDRH3 WGPYYGYAMDY 22CDRL1 SASSSVTYMH23 CDRL2 DTSRLAP 24 CDRL3 HQWSTYPPT Table 2: VH CHAIN AMINO ACID SEQUENCES SEQ ID NO AMINO ACID SEQUENCE QVQLVQSGAELKKPGASVKVSCKASGFTFTRYWWHWVRQ 1 APGKGLEWIGRIDPNSGTTRFIEKFKTRATITVDKSTSTAYMH LSSLRSEDSAVYYCARWGPYYGYAMDYWGQGTSVTVSS QVQLVQSGAELKKPGASVKVSCKASGFTFTRYWWHWVRQAP 2 GKGLEWIGRIDPNSGTTRFIEKFKTRATITVDKSTSTAYMELSS LRSEDSAVYYCARWGPYYGYAMDYWGQGTSVTVSS QVQLVQSGAEVKKPGASVKVSCKASGFTFTRYWWHWVR 3 QAPGKGLEWIGRIDPNSGTTRFIEKFKTRATITVDKSTSTAYM ELSSLRSEDTAVYYCARWGPYYGYAMDYWGQGTLVTVSS QVQLVQSGAEVKKPGASVKVSCKASGFTFTRYWWHWVR 4 QAPGKGLEWIGRIDPNSGTTRFIEKFKTRVTITVDKSTSTAYM ELSSLRSEDTAVYYCARWGPYYGYAMDYWGQGTLVTVSS Table 3: VL CHAIN AMINO ACID SEQUENCES SEQ ID NO AMINO ACID SEQUENCE QIVLTQSPAILSLSPGERVTITCSASSSVTYMHWYQQKLGKA 5 PKLWIYDTSRLAPGSPARFSGSGSGTDYTLTISSLETEDFASYF CHQWSTYPPTFGQGTKLEIK QIVLTQSPATLSLSPGERVTITCSASSSVTYMHWYQQKLGKAP 6 KLWIYDTSRLAPGSPARFSGSGSGTDYTLTISSLESEDFASYFCH QWSTYPPTFGQGTKLEIK QIVLTQSPATLSLSPGERVTITCSASSSVTYMHWYQQKPGK 7 APKLWIYDTSRLAPGSPARFSGSGSGTDYTLTISSLESEDFASY FCHQWSTYPPTFGQGTKLEIK QIVLTQSPATLSLSPGERVTITCSASSSVTYMHWYQQKPGKAP 8 KLWIYDTSRLAPGSPARFSGSGSGTDYTLTISSLESEDFATYFC HQWSTYPPTFGQGTKLEIK QIVLTQSPATLSLSPGERVTITCSASSSVTYMHWYQQKPGKAP 9 KLLIYDTSRLAPGSPARFSGSGSGTDYTLTISSLESEDFATYFCH QWSTYPPTFGQGTKLEIK Table 4: HEAVY CHAIN AND LIGHT CHAIN AMINO ACID SEQUENCES SEQ ID NO AMINO ACID SEQUENCE QVQLVQSGAELKKPGASVKVSCKASGFTFTRYWWHWVRQ 15 APGKGLEWIGRIDPNSGTTRFIEKFKTRATITVDKSTSTAYM ELSSLRSEDSAVYYCARWGPYYGYAMDYWGQGTSVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKC KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GK QIVLTQSPATLSLSPGERVTITCSASSSVTYMHWYQQKPGKA 16 PKLLIYDTSRLAPGSPARFSGSGSGTDYTLTISSLESEDFATYF CHQWSTYPPTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGT ASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGEC In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 5, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 6, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 7, respectively. In some embodiments, the humanized anti- SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 8, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 9, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 5, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 6, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 7, respectively. In some embodiments, the humanized anti- SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 8, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 9, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 3 and SEQ ID NO: 5, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 3 and SEQ ID NO: 6, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 3 and SEQ ID NO: 7, respectively. In some embodiments, the humanized anti- SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 3 and SEQ ID NO: 8, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 3 and SEQ ID NO: 9, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 4 and SEQ ID NO: 5, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 4 and SEQ ID NO: 6, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 4 and SEQ ID NO: 7, respectively. In some embodiments, the humanized anti- SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 4 and SEQ ID NO: 8, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 4 and SEQ ID NO: 9, respectively. In some embodiments, the humanized anti-SFRP2 comprises a variable heavy (VH) chain polypeptide and a variable light (VL) chain polypeptide comprising the amino acid sequences of SEQ ID NO: 15 and SEQ ID NO: 16, respectively. In some aspects, an anti-SFRP2 antibody or antigen binding fragment thereof comprises a chimeric antibody. In some aspects, an anti-SFRP2 antibody or antigen binding fragment thereof comprises a chimeric antibody specific for binding to an epitope of SFRP2. In some embodiments, the epitope of SFRP2 is NDFALKIKVKEITYINRDT (SEQ ID NO:14). In some aspects, a chimeric anti-SFRP2 antibody comprises a VH chain polypeptide of: QVQLQQPGAELVQPGASVMLSCKASGFTFTRYWWHWVRQTPGR GLEWIGRIDPNSGTTRFIEKFKTKATLTVDKPSSTAYMHLSSLTSEDSAVYYCAR WGPYYGYAMDYWGPGTSVTVSS (SEQ ID NO: 10) and a VL chain polypeptide of: QIVLTQSPAIMSASPGQKVTITCSASSSVTYMHWYQQKLGSSPKL WIYDTSRLAPGSPARFSGSGSGTSYSLTISSMETEDAASYFCHQWSTYPPTFGTGT KLEIQ (SEQ ID NO: 11). In some aspects, a chimeric anti-SFRP2 antibody comprises a VH chain polypeptide of SEQ ID NO: 10 and a VL chain polypeptide of: QIVLTQSPAIMSASPGQKVTITCSASSSVTYMHWYQQKLGSSPKL WIYDTSRLAPGSPARFSGSGSGTSYSLTISSMETEDAASYFCHQWSTYPPTFGTGT KLEIK (SEQ ID NO: 13). In some aspects, a chimeric anti-SFRP2 antibody comprises human constant regions, such as any of those discussed herein. In some instances, a chimeric anti-SFRP2 antibody comprises an IgGI constant region. In some embodiments, the anti-SFRP2 antibody heavy chain comprises a sequence of SEQ ID NO: 15. In some aspects, the heavy chain is encoded by a polynucleotide sequence of SEQ ID NO:17: caggtccaactggtgcagtctggggctgagcttaaaaagcctggggcttcagtgaaggtgtcctgcaaggcttctggcttcacct tcacccgctactggtggcactgggtgcgccaggcccctggaaagggccttgagtggattggaaggattgatcctaatagtggta ccactcgcttcatcgagaagttcaagacccgcgccacaatcactgtagacaaatccaccagcacagcctacatggaactcagca gcctgcgctctgaggactctgcggtctattattgtgcaagatggggaccttattacggctatgctatggactactggggtcaagga acctcagtcaccgtctcctcagcctccaccaagggcccatcggtcttccccctggcaccctctagcaagagcacctctgggggc acagcggccctgggctgcctggtcaaggactacttccccgaaccggtgacggtgtcgtggaactcaggcgccctgaccagcg gcgtgcacaccttcccggctgtcctacagtcctcaggactctactccctcagcagcgtggtgaccgtgccctccagcagcttggg cacccagacctacatctgcaacgtgaatcacaagcccagcaacaccaaggtggacaagaaagttgagcccaaatcttgtgaca aaactcacacatgcccaccgtgcccagcacctgaactcctggggggaccgtcagtcttcctcttccccccaaaacccaaggaca ccctcatgatctcccggacccctgaggtcacatgcgtggtggtggacgtgagccacgaagaccctgaggtcaagttcaactggt acgtggacggcgtggaggtgcataatgccaagacaaagccgcgggaggagcagtacaacagcacgtaccgtgtggtcagcg tcctcaccgtcctgcaccaggactggctgaatggcaaggagtacaagtgcaaggtctccaacaaagccctcccagcccccatc gagaaaaccatctccaaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccatcccgggatgagctgacc aagaaccaggtcagcctgacctgcctggtcaaaggcttctatcccagcgacatcgccgtggagtgggagagcaatgggcagc cggagaacaactacaagaccacgcctcccgtgctggactccgacggctccttcttcctctatagcaagctcaccgtggacaaga gcaggtggcagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcacaaccactacacgcagaagagcctctcc ctgtctcccgggaaatga. In some embodiments, the anti-SFRP2 antibody light chain comprises a sequence of SEQ ID NO: 16. In some aspects, the light chain is encoded by a polynucleotide sequence of SEQ ID NO:18: Caaattgttctcacccagtctccagcaaccctgtctttgtctcctggggaaagagtcaccataacctgcagtgccagctcaagtg taacctacatgcactggtaccagcagaagccaggcaaagcccccaaactcttgatttatgacacatcccggctggctcctggat ctcctgctcgcttctccggcagtgggtctgggaccgactacaccctcacaatcagcagcctagagtctgaagatttcgccactta tttctgccatcagtggagtacctacccacccacgttcggtcaggggaccaagctggagatcaaacgaactgtggctgcaccat ctgtcttcatcttcccgccatctgatgagcagcttaagtccggaactgctagcgttgtgtgcctgctgaataacttctatcccagag aggccaaagtacagtggaaggtggataacgccctccaatcgggaaactcccaggagagtgtcacagagcaggacagcaag gacagcacctacagcctcagcagcaccctgacgctgagcaaagcagactacgagaaacacaaagtctacgcctgcgaagtc acccatcagggcctgagctcgcccgtcacaaagagcttcaacaggggagagtgttag. Method of Diagnosing a Disease or Disorder In some embodiments, the present invention relates, in part, to a method of diagnosing a disease or disorder associated with an increased level of KRAS signaling or SFRP2 in a subject in need thereof. In one aspect, the present invention provides a method of diagnosing pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer in a subject, the method comprising assessing the level of KRAS signaling or SFRP2 in the subject, wherein an increased level of KRAS signaling or SFRP2 is associated with pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer. In some embodiments, the subject is diagnosed with a disease or disorder when the level of KRAS signaling or SFRP2, or the combination thereof, is increased above a threshold level (e.g., a predetermined threshold level). In some embodiments, the threshold level is obtained from control group samples. In some embodiments, the subject is diagnosed with a disease or disorder by detecting an increased level of KRAS signaling or SFRP2, or the combination thereof, relative to a control level. In some embodiments, the control level is a level of KRAS signaling or SFRP2, or the combination thereof, in a subject or population known not to have the disease. In various embodiments of the methods of the invention, the level of KRAS signaling or SFRP2, or the combination thereof, is determined to be increased or to be higher when the level of KRAS signaling or SFRP2, or the combination thereof, is determined to be increased by at least 0.01 fold, at least 0.05 fold, at least 0.07 fold, at least 0.076 fold, at least 0.1 fold, at least 0.18 fold, at least 0.19 fold, at least 0.3 fold, at least 0.36 fold, at least 0.37 fold, at least 0.38 fold, at least 0.4 fold, at least 0.43 fold, at least 1 fold, at least 1.1 fold, at least 1.2 fold, at least 1.3 fold, at least 1.4 fold, at least 1.5 fold, at least 1.6 fold, at least 1.7 fold, at least 1.8 fold, at least 1.9 fold, at least 2 fold, at least 2.1 fold, at least 2.2 fold, at least 2.3 fold, at least 2.4 fold, at least 2.5 fold, at least 2.6 fold, at least 2.7 fold, at least 2.8 fold, at least 2.9 fold, at least 3 fold, at least 3.5 fold, at least 4 fold, at least 4.5 fold, at least 5 fold, at least 5.5 fold, at least 6 fold, at least 6.5 fold, at least 7 fold, at least 7.5 fold, at least 8 fold, at least 8.5 fold, at least 9 fold, at least 9.5 fold, at least 10 fold, at least 11 fold, at least 12 fold, at least 13 fold, at least 14 fold, at least 15 fold, at least 16 fold, at least 16.3 fold, at least 16.31 fold, at least 20 fold, at least 25 fold, at least 26 fold, at least 26.7 fold, at least 26.72 fold, at least 30 fold, at least 40 fold, at least 50 fold, at least 75 fold, at least 100 fold, at least 192 fold, at least 192.4 fold, at least 192.44 fold, at least 200 fold, at least 250 fold, at least 500 fold, or at least 1000 fold, or at least 10000 fold, when compared with a comparator control or threshold level. In some embodiments, the subject is diagnosed with a disease or disorder when the level of KRAS signaling or KRAS is increased or higher as compared to a comparator (e.g., a predetermined threshold level or the normal level in a healthy population). In some embodiments, the subject is diagnosed with a disease or disorder when the level of SFRP2 is increased or higher as compared to a comparator (e.g., a predetermined threshold level or the normal level in a healthy population). In some embodiments, the subject is diagnosed with a disease or disorder when the level of SFRP2 is increased or higher as compared to a comparator (e.g., a predetermined threshold level or the normal level in a healthy population) and the level of KRAS signaling or KRAS is increased or higher as compared to a comparator (e.g., a predetermined threshold level or the normal level in a healthy population). For example, in some embodiments, the subject is diagnosed with a disease or disorder when the level of KRAS, KRAS signaling or SFRP2, or the combination of KRAS / KRAS signaling and SFRP2 is increased by at least 0.01 fold, or at least 0.18 fold. In some embodiments, the subject is diagnosed with a disease or disorder when the level of KRAS, KRAS signaling or SFRP2, or the combination of KRAS / KRAS signaling and SFRP2 is increased in a range from 0.1 fold to 10,000 fold. In one aspect, the present invention provides a method of evaluating the effectiveness of a treatment for a disease or disorder in a subject, the method comprising assessing the level KRAS, KRAS signaling or SFRP2, or the combination of KRAS / KRAS signaling and SFRP2 in a biological sample from the subject, wherein the level of KRAS signaling and / or SFRP2 is associated with the disease or disorder according to the methods described elsewhere herein. In one aspect, the present invention provides a method of evaluating the effectiveness of a treatment for a disease or disorder in a subject, the method comprising detecting the level of KRAS, KRAS signaling or SFRP2, or the combination of KRAS / KRAS signaling and SFRP2, in a subject pre administration of a treatment regimen, post administration of a treatment regimen, or both pre- and post- administration of a treatment regimen. For example, in one embodiment, the treatment regimen comprises administration of an antibody, and the method of the invention is used to evaluate the effectiveness of the treatment regimen by detecting the level of KRAS signaling and / or SFRP2 following treatment. In some embodiments, the treatment regimen comprises administering a therapeutic agent to reduce or eliminate KRAS signaling and / or SFRP2, and the method of the invention is used to evaluate the effectiveness of the treatment regimen by detecting the absence of or a reduced level of KRAS signaling and / or SFRP2 following treatment. Method of Preventing or Treating a Disease or Disorder The present invention further relates, in part, to methods of preventing or treating a diseases or disorders associated with an increased level of KRAS signaling and / or SFRP2 in a subject in need thereof. In one aspect, the method comprises administering a therapeutic agent to the subject. In some embodiments, the therapeutic agent reduces the level (e.g., activity, amount, concentration, expression, level, etc.) of KRAS signaling or SFRP2 according to the method of the present invention. In some embodiments, the therapeutic agent is administered to a subject diagnosed as having a disease or disorder associated with an increased level of KRAS signaling or SFRP2. In one aspect, the present invention relates to a method of preventing or treating a disease or disorder associated with an increased level of KRAS signaling or SFRP2 in a subject in need thereof. In some embodiments, the method comprises administering a treatment to reduce the level (e.g., activity, amount, concentration, expression, level, etc.) of KRAS signaling or SFRP2 according to the method of the present invention in the subject. In some embodiments, the treatment comprises inhibiting KRAS signaling or SFRP2. In some embodiments, the treatment comprises administering a therapeutically effective amount of an inhibitor of KRAS signaling or SFRP2. For example, in some embodiments, the inhibitor of KRAS signaling or SFRP2 is an antibody, nucleic acid, peptide, small molecule, antagonist, aptamer, peptidomimetic, or a combination thereof. In some embodiments, the invention relates to a method of administering a SFRP2 inhibitor to a subject having increased KRAS or KRAS signaling for the treatment or prevention of a disease or disorder. Therefore, in some embodiments, the invention includes methods of detecting an increased level of KRAS signaling in a sample from a subject, and administering to the subject an inhibitor of SFRP2 for the treatment or prevention of a disease or disorder associated with increased KRAS or KRAS signaling. In one aspect, the present invention relates to a method of preventing or treating pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer in a subject in need thereof. In some embodiments, the method comprises administering a treatment to decrease the level (e.g., activity, amount, concentration, expression, level, etc.) of KRAS signaling or SFRP2 in the subject. In some embodiments, the treatment comprises administering a therapeutically effective amount of an inhibitor of KRAS signaling or SFRP2, or a combination thereof. For example, in some embodiments, the inhibitor of KRAS signaling or SFRP2 is a nucleic acid, an antisense nucleic acid molecule (e.g., siRNA), a peptide, an antibody, a small molecule, or a combination thereof. In some embodiments, the method of preventing or treating pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer comprises administering a treatment to the subject for inhibiting the level or activity of KRAS or SFRP2 or any combination thereof, or administering an antibody that binds to KRAS or SFRP2, or a combination thereof. Examples of KRAS inhibitors include, but are not limited to, Sotorasib, adagrasib and MRTX1133. Examples of SFRP2 inhibitors include, but are not limited to, anti-SFRP2 antibodies as described in U.S. Patent Application No.17 / 547,550, the contents of which is incorporated herein in its entirety. In some embodiments, the inhibitors of the invention inhibit a combination of KRAS and SFRP2. In some embodiments, the invention provides a combination of inhibitors that inhibits a combination of KRAS and SFRP2. For example, in some embodiments, the combination of inhibitors is a combination of a) Sotorasib, adagrasib or MRTX1133 and b) an anti-SFRP2 antibody. In some embodiments, the invention provides a single inhibitor that inhibits a combination of KRAS and SFRP2. Exemplary single inhibitors that inhibit a combination of KRAS and SFRP2 include, but are not limited to bispecific antibodies, where the first specificity is to KRAS and the second specificity is to SFRP2. In some embodiments, the inhibitor can be administered in combination with one or more additional therapeutic agent. Additional therapeutic agents include, but are not limited to cytotoxic / anti-neoplastic agents, anti-angiogenic agents, or other anti- cancer agents. Cytotoxic / anti-neoplastic agents are defined as agents which attack and kill cancer cells. Some cytotoxic / anti-neoplastic agents are alkylating agents, which alkylate the genetic material in tumor cells, e.g., cis-platin, cyclophosphamide, nitrogen mustard, trimethylene thiophosphoramide, carmustine, busulfan, chlorambucil, belustine, uracil mustard, chlomaphazin, and dacabazine. Other cytotoxic / anti-neoplastic agents are antimetabolites for tumor cells, e.g., cytosine arabinoside, fluorouracil, methotrexate, mercaptopuirine, azathioprime, and procarbazine. Other cytotoxic / anti-neoplastic agents are antibiotics, e.g., doxorubicin, bleomycin, dactinomycin, daunorubicin, mithramycin, mitomycin, mytomycin C, and daunomycin. There are numerous liposomal formulations commercially available for these compounds. Still other cytotoxic / anti-neoplastic agents are mitotic inhibitors (vinca alkaloids). These include vincristine, vinblastine and etoposide. Miscellaneous cytotoxic / anti-neoplastic agents include taxol and its derivatives, L-asparaginase, anti-tumor antibodies, dacarbazine, azacytidine, amsacrine, melphalan, VM-26, ifosfamide, mitoxantrone, and vindesine. Anti-angiogenic agents are well known to those of skill in the art. Suitable anti-angiogenic agents for use in the methods of the present disclosure include anti- VEGF antibodies, including humanized and chimeric antibodies, anti-VEGF aptamers and antisense oligonucleotides. Other known inhibitors of angiogenesis include angiostatin, endostatin, interferons, interleukin 1 (including alpha and beta) interleukin 12, retinoic acid, and tissue inhibitors of metalloproteinase-1 and -2. (TIMP-1 and -2). Small molecules, including topoisomerases such as razoxane, a topoisomerase II inhibitor with anti-angiogenic activity, can also be used. Other anti-cancer agents that can be used in combination with the disclosed inhibitors include, but are not limited to: acivicin; aclarubicin; acodazole hydrochloride; acronine; adozelesin; aldesleukin; altretamine; ambomycin; ametantrone acetate; aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacitidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnafide dimesylate; bizelesin; bleomycin sulfate; brequinar sodium; bropirimine; busulfan; cactinomycin; calusterone; caracemide; carbetimer; carboplatin; carmustine; carubicin hydrochloride; carzelesin; cedefingol; chlorambucil; cirolemycin; cisplatin; cladribine; crisnatol mesylate; cyclophosphamide; cytarabine; dacarbazine; dactinomycin; daunorubicin hydrochloride; decitabine; dexormaplatin; dezaguanine; dezaguanine mesylate; diaziquone; docetaxel; doxorubicin; doxorubicin hydrochloride; droloxifene; droloxifene citrate; dromostanolone propionate; duazomycin; edatrexate; eflornithine hydrochloride; elsamitrucin; enloplatin; enpromate; epipropidine; epirubicin hydrochloride; erbulozole; esorubicin hydrochloride; estramustine; estramustine phosphate sodium; etanidazole; etoposide; etoposide phosphate; etoprine; fadrozole hydrochloride; fazarabine; fenretinide; floxuridine; fludarabine phosphate; fluorouracil; fluorocitabine; fosquidone; fostriecin sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride; ifosfamide; ilmofosine; interleukin II (including recombinant interleukin II, or rIL2), interferon alfa-2a; interferon alfa-2b; interferon alfa- n1; interferon alfa-n3; interferon beta-I a; interferon gamma-I b; iproplatin; irinotecan hydrochloride; lanreotide acetate; letrozole; leuprolide acetate; liarozole hydrochloride; lometrexol sodium; lomustine; losoxantrone hydrochloride; masoprocol; maytansine; mechlorethamine hydrochloride; megestrol acetate; melengestrol acetate; melphalan; menogaril; mercaptopurine; methotrexate; methotrexate sodium; metoprine; meturedepa; mitindomide; mitocarcin; mitocromin; mitogillin; mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone hydrochloride; mycophenolic acid; nocodazole; nogalamycin; ormaplatin; oxisuran; paclitaxel; pegaspargase; peliomycin; pentamustine; peplomycin sulfate; perfosfamide; pipobroman; piposulfan; piroxantrone hydrochloride; plicamycin; plomestane; porfimer sodium; porfiromycin; prednimustine; procarbazine hydrochloride; puromycin; puromycin hydrochloride; pyrazofurin; riboprine; rogletimide; safingol; safingol hydrochloride; semustine; simtrazene; sparfosate sodium; sparsomycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin; sulofenur; talisomycin; tecogalan sodium; tegafur; teloxantrone hydrochloride; temoporfin; teniposide; teroxirone; testolactone; thiamiprine; thioguanine; thiotepa; tiazofurin; tirapazamine; toremifene citrate; trestolone acetate; triciribine phosphate; trimetrexate; trimetrexate glucuronate; triptorelin; tubulozole hydrochloride; uracil mustard; uredepa; vapreotide; verteporfin; vinblastine sulfate; vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate; vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate; vinrosidine sulfate; vinzolidine sulfate; vorozole; zeniplatin; zinostatin; zorubicin hydrochloride. Other anti-cancer drugs include, but are not limited to: 20-epi-1,25 dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; aclarubicin; acylfulvene; adecypenol; adozelesin; aldesleukin; ALL-TK antagonists; altretamine; ambamustine; amidox; amifostine; aminolevulinic acid; amrubicin; amsacrine; anagrelide; anastrozole; andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-dorsalizing morphogenetic protein-1; antiandrogen, prostatic carcinoma; antiestrogen; antineoplaston; antisense oligonucleotides; aphidicolin glycinate; apoptosis gene modulators; apoptosis regulators; apurinic acid; ara-CDP-DL- PTBA; arginine deaminase; asulacrine; atamestane; atrimustine; axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxin; azatyrosine; baccatin III derivatives; balanol; batimastat; BCR / ABL antagonists; benzochlorins; benzoylstaurosporine; beta lactam derivatives; beta-alethine; betaclamycin B; betulinic acid; bFGF inhibitor; bicalutamide; bisantrene; bisaziridinylspermine; bisnafide; bistratene A; bizelesin; breflate; bropirimine; budotitane; buthionine sulfoximine; calcipotriol; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carboxamide-amino-triazole; carboxyamidotriazole; CaRest M3; CARN 700; cartilage derived inhibitor; carzelesin; casein kinase inhibitors (ICOS); castanospermine; cecropin B; cetrorelix; chlorins; chloroquinoxaline sulfonamide; cicaprost; cis-porphyrin; cladribine; clomifene analogues; clotrimazole; collismycin A; collismycin B; combretastatin A4; combretastatin analogue; conagenin; crambescidin 816; crisnatol; cryptophycin 8; cryptophycin A derivatives; curacin A; cyclopentanthraquinones; cycloplatam; cypemycin; cytarabine ocfosfate; cytolytic factor; cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslorelin; dexamethasone; dexifosfamide; dexrazoxane; dexverapamil; diaziquone; didemnin B; didox; diethylnorspermine; dihydro-5- azacytidine; dihydrotaxol, 9-; dioxamycin; diphenyl spiromustine; docetaxel; docosanol; dolasetron; doxifluridine; droloxifene; dronabinol; duocarmycin SA; ebselen; ecomustine; edelfosine; edrecolomab; eflornithine; elemene; emitefur; epirubicin; epristeride; estramustine analogue; estrogen agonists; estrogen antagonists; etanidazole; etoposide phosphate; exemestane; fadrozole; fazarabine; fenretinide; filgrastim; finasteride; flavopiridol; flezelastine; fluasterone; fludarabine; fluorodaunorunicin hydrochloride; forfenimex; formestane; fostriecin; fotemustine; gadolinium texaphyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitors; gemcitabine; glutathione inhibitors; hepsulfam; heregulin; hexamethylene bisacetamide; hypericin; ibandronic acid; idarubicin; idoxifene; idramantone; ilmofosine; ilomastat; imidazoacridones; imiquimod; immunostimulant peptides; insulin-like growth factor-1 receptor inhibitor; interferon agonists; interferons; interleukins; iobenguane; iododoxorubicin; ipomeanol, 4- ; iroplact; irsogladine; isobengazole; isohomohalicondrin B; itasetron; jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide; leinamycin; lenograstim; lentinan sulfate; leptolstatin; letrozole; leukemia inhibiting factor; leukocyte alpha interferon; leuprolide+estrogen+progesterone; leuprorelin; levamisole; liarozole; linear polyamine analogue; lipophilic disaccharide peptide; lipophilic platinum compounds; lissoclinamide 7; lobaplatin; lombricine; lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine; lurtotecan; lutetium texaphyrin; lysofylline; lytic peptides; maitansine; mannostatin A; marimastat; masoprocol; maspin; matrilysin inhibitors; matrix metalloproteinase inhibitors; menogaril; merbarone; meterelin; methioninase; metoclopramide; MIF inhibitor; mifepristone; miltefosine; mirimostim; mismatched double stranded RNA; mitoguazone; mitolactol; mitomycin analogues; mitonafide; mitotoxin fibroblast growth factor-saporin; mitoxantrone; mofarotene; molgramostim; monoclonal antibody, human chorionic gonadotrophin; monophosphoryl lipid A+myobacterium cell wall sk; mopidamol; multiple drug resistance gene inhibitor; multiple tumor suppressor 1-based therapy; mustard anticancer agent; mycaperoxide B; mycobacterial cell wall extract; myriaporone; N-acetyldinaline; N-substituted benzamides; nafarelin; nagrestip; naloxone+pentazocine; napavin; naphterpin; nartograstim; nedaplatin; nemorubicin; neridronic acid; neutral endopeptidase; nilutamide; nisamycin; nitric oxide modulators; nitroxide antioxidant; nitrullyn; O6-benzylguanine; octreotide; okicenone; oligonucleotides; onapristone; ondansetron; ondansetron; oracin; oral cytokine inducer; ormaplatin; osaterone; oxaliplatin; oxaunomycin; paclitaxel; paclitaxel analogues; paclitaxel derivatives; palauamine; palmitoylrhizoxin; pamidronic acid; panaxytriol; panomifene; parabactin; pazelliptine; pegaspargase; peldesine; pentosan polysulfate sodium; pentostatin; pentrozole; perflubron; perfosfamide; perillyl alcohol; phenazinomycin; phenylacetate; phosphatase inhibitors; picibanil; pilocarpine hydrochloride; pirarubicin; piritrexim; placetin A; placetin B; plasminogen activator inhibitor; platinum complex; platinum compounds; platinum-triamine complex; porfimer sodium; porfiromycin; prednisone; propyl bis-acridone; prostaglandin J2; proteasome inhibitors; protein A-based immune modulator; protein kinase C inhibitor; protein kinase C inhibitors, microalgal; protein tyrosine phosphatase inhibitors; purine nucleoside phosphorylase inhibitors; purpurins; pyrazoloacridine; pyridoxylated hemoglobin polyoxyethylene conjugate; raf antagonists; raltitrexed; ramosetron; ras farnesyl protein transferase inhibitors; ras inhibitors; ras-GAP inhibitor; retelliptine demethylated; rhenium Re 186 etidronate; rhizoxin; ribozymes; RII retinamide; rogletimide; rohitukine; romurtide; roquinimex; rubiginone B1; ruboxyl; safingol; saintopin; SarCNU; sarcophytol A; sargramostim; Sdi 1 mimetics; semustine; senescence derived inhibitor 1; sense oligonucleotides; signal transduction inhibitors; signal transduction modulators; single chain antigen binding protein; sizofuran; sobuzoxane; sodium borocaptate; sodium phenylacetate; solverol; somatomedin binding protein; sonermin; sparfosic acid; spicamycin D; spiromustine; splenopentin; spongistatin 1; squalamine; stem cell inhibitor; stem-cell division inhibitors; stipiamide; stromelysin inhibitors; sulfinosine; superactive vasoactive intestinal peptide antagonist; suradista; suramin; swainsonine; synthetic glycosaminoglycans; tallimustine; tamoxifen methiodide; tauromustine; tazarotene; tecogalan sodium; tegafur; tellurapyrylium; telomerase inhibitors; temoporfin; temozolomide; teniposide; tetrachlorodecaoxide; tetrazomine; thaliblastine; thiocoraline; thrombopoietin; thrombopoietin mimetic; thymalfasin; thymopoietin receptor agonist; thymotrinan; thyroid stimulating hormone; tin ethyl etiopurpurin; tirapazamine; titanocene bichloride; topsentin; toremifene; totipotent stem cell factor; translation inhibitors; tretinoin; triacetyluridine; triciribine; trimetrexate; triptorelin; tropisetron; turosteride; tyrosine kinase inhibitors; tyrphostins; UBC inhibitors; ubenimex; urogenital sinus-derived growth inhibitory factor; urokinase receptor antagonists; vapreotide; variolin B; vector system, erythrocyte gene therapy; velaresol; veramine; verdins; verteporfin; vinorelbine; vinxaltine; vitaxin; vorozole; zanoterone; zeniplatin; zilascorb; and zinostatin stimalamer. In some embodiments, the anti-cancer drug is 5-fluorouracil, taxol, or leucovorin. In some embodiments, the anti-cancer agent may be a prodrug form of an anti-cancer agent. As used herein, the term “prodrug form” and its derivatives is used to refer to a drug that has been chemically modified to add and / or remove one or more substituents in such a manner that, upon introduction of the prodrug form into a subject, such a modification may be reversed by naturally occurring processes, thus reproducing the drug. The use of a prodrug form of an anti-cancer agent in the compositions, among other things, may increase the concentration of the anti-cancer agent in the compositions of the present disclosure. In certain embodiments, an anti-cancer agent may be chemically modified with an alkyl or acyl group or some form of lipid. The selection of such a chemical modification, including the substituent(s) to add and / or remove to create the prodrug, may depend upon a number of factors including, but not limited to, the particular drug and the desired properties of the prodrug. One of ordinary skill in the art, with the benefit of this disclosure, will recognize suitable chemical modifications. In some embodiments, the treatment comprises administering a therapeutically effective amount of at least one inhibitor of KRAS, SFRP2, or a combination thereof. In some embodiments, the treatment comprises decreasing or eliminating KRAS signaling, SFRP2, or a combination thereof, by administering a therapeutically effective amount of an inhibitor of KRAS, SFRP2, or a combination thereof. Any drug or any combination of drugs disclosed herein may be administered to a subject to treat the disease or disorder. The drugs herein can be formulated in any number of ways, often according to various known formulations in the art or as disclosed or referenced herein. In various embodiments, one or more additional drugs may be optionally administered in addition to those that are recommended or have been administered. An additional drug will typically not be any drug that is not recommended or that should be avoided. Method of Assessing the Prognosis, Assessing the Effectiveness, or Alleviating the Toxicity of Treatment of a Disease or Disorder The present invention further relates, in part, to a method of assessing the prognosis or assessing the effectiveness of treatment of a disease or disorder associated with KRAS signaling or SFRP2 in a subject in need thereof. In one aspect, the present invention provides a method of assessing the prognosis or assessing the effectiveness of treatment of a disease or disorder in a subject, the method comprising assessing KRAS signaling or the level or activity of SFRP2 in the subject, wherein KRAS signaling or the level or activity of SFRP2 is identified to be associated with the disease or disorder according to the method described above. In one aspect, the present invention provides a method of assessing the prognosis or assessing the effectiveness of treatment for pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer in a subject, the method comprising assessing the level or activity of KRAS signaling or the level or activity of SFRP2 in the subject. In some embodiments the pancreatic cancer is pancreatic adenocarcinoma. In some embodiments, the disease or disorder is lung cancer. In some embodiments, the method of assessing the prognosis or assessing the effectiveness of treatment of a disease or disorder comprises comparing the level of KRAS signaling or the level or activity of SFRP2, that is identified to be associated with the disease or disorder according to the method described above, to a threshold level. In some embodiments, the threshold level is obtained from control group samples. The present invention further relates, in part, to a method of assessing the prognosis or assessing the effectiveness of treatment of a disease or disorder associated with KRAS signaling or the level or activity of SFRP2 in a subject in need thereof. In one aspect, the present invention provides a method of assessing the prognosis or assessing the effectiveness of treatment for pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer in a subject, the method comprising assessing KRAS signaling or the level or activity of SFRP2 in the subject. In some embodiments, the treatment can include, but is not limited to, chemotherapy or angiogenic treatments. In some embodiments, a decrease in KRAS signaling or the level or activity of SFRP2 in the subject indicates that the treatment is effective. In some embodiments, no change in KRAS signaling or the level or activity of SFRP2 in the subject indicates that the treatment is not effective, and that the treatment should be discontinued. In some embodiments, the method of assessing the prognosis or assessing the effectiveness of treatment of a disease or disorder comprises comparing the level of KRAS signaling or the level or activity of SFRP2, that is identified to be associated with the disease or disorder according to the method described above, to a threshold level. In some embodiments, the threshold level is obtained from control group samples. In some embodiments, the threshold level is obtained from a sample of a subject obtained prior to administration of a therapeutic agent. In another aspect, the present invention provides a method of predicting a response to a treatment. Information obtained from the methods of the invention described herein can be used alone, or in combination with other information (e.g., age, family history, disease status, disease history, vital signs, blood chemistry, PSA level, Gleason score, primary tumor staging, lymph node staging, metastasis staging, expression of other gene signatures relevant to outcomes of a disease or disorder, such as autoimmune disease or disorder, cancer, inflammatory disease or disorder, metabolic disease or disorder, neurodegenerative disease or disorder, organ tissue rejection, organ transplant rejection, or any combination thereof, etc.) from the subject or from the biological sample obtained from the subject. Compositions The present invention also provides various pharmaceutical compositions comprising an inhibitor of the present invention. In some embodiments, the composition of the invention inhibits KRAS signaling or SFRP2. In various aspects, the composition comprises: one or more inhibitor of the present invention and one or more stabilizers. In various embodiments, the stabilizer to compound weight ratio is less than 50%. In some embodiments, the stabilizer comprises a biocompatible polymer. Examples of stabilizers include, but are not limited to, biocompatible polymer, a biodegradable polymer, a multifunctional linker, starch, modified starch, and starch derivatives, gums, including but not limited to polymers, polypeptides, albumin, amino acids, thiols, amines, carboxylic acid and combinations or derivatives thereof, citric acid, xanthan gum, alginic acid, other alginates, benitoniite, veegum, agar, guar, locust bean gum, gum arabic, quince psyllium, flax seed, okra gum, arabinoglactin, pectin, tragacanth, scleroglucan, dextran, amylose, amylopectin, dextrin, etc., cross-linked polyvinylpyrrolidone, ion-exchange resins, potassium polymethacrylate, carrageenan (and derivatives), gum karaya and biosynthetic gum, polycarbonates (linear polyesters of carbonic acid); microporous materials (bisphenol, a microporous poly(vinylchloride), micro-porous polyamides, microporous modacrylic copolymers, microporous styrene-acrylic and its copolymers); porous polysulfones, halogenated poly(vinylidene), polychloroethers, acetal polymers, polyesters prepared by esterification of a dicarboxylic acid or anhydride with an alkylene polyol, poly(alkylenesulfides), phenolics, polyesters, asymmetric porous polymers, cross-linked olefin polymers, hydrophilic microporous homopolymers, copolymers or interpolymers having a reduced bulk density, and other similar materials, poly(urethane), cross-linked chain-extended poly(urethane), poly(imides), poly(benzimidazoles), collodion, regenerated proteins, semi-solid cross-linked poly(vinylpyrrolidone), monomeric, dimeric, oligomeric or long-chain, copolymers, block polymers, block co-polymers, polymers, PEG, dextran, modified dextran, polyvinylalcohol, polyvinylpyrollidone, polyacrylates, polymethacrylates, polyanhydrides, polypeptides, albumin, alginates, amino acids, thiols, amines, carboxylic acids, or combinations thereof. The compositions may be formulated in a pharmaceutically acceptable excipient, such as wetting agents, buffers, disintegrants, binders, fillers, flavoring agents and liquid carrier media such as sterile water, water / ethanol etc. The compositions should be suitable for administration either by topical administration or injection or inhalation or catheterization or instillation or transdermal introduction into any of the various body cavities including the alimentary canal, the vagina, the rectum, the bladder, the ureter, the urethra, the mouth, etc. For oral administration, the pH of the composition is preferably in the acid range (e.g., 2 to 7) and buffers or pH adjusting agents may be used. The contrast media may be formulated in conventional pharmaceutical administration forms, such as tablets, capsules, powders, solutions, dispersion, syrups, suppositories etc. The compositions of the invention can be formulated and administered to a subject, as now described. The invention encompasses the preparation and use of pharmaceutical compositions comprising the compositions of the invention useful for the delivery of a therapeutic agent to a cell. The invention also encompasses the preparation and use of pharmaceutical compositions comprising the compositions of the invention useful for the treatment of a disease or disorder. The invention also encompasses the preparation and use of pharmaceutical compositions comprising the compositions of the invention useful for improved cell penetration. Such a pharmaceutical composition may consist of the active ingredient alone, in a form suitable for administration to a subject, or the pharmaceutical composition may comprise the active ingredient and one or more pharmaceutically acceptable carriers, one or more additional ingredients, or some combination of these. The active ingredient may be present in the pharmaceutical composition in the form of a physiologically acceptable ester or salt, such as in combination with a physiologically acceptable cation or anion, as is well known in the art. In various embodiments, the pharmaceutical compositions useful in the methods of the invention may be administered, by way of example, systemically, parenterally, or topically, such as, in oral formulations, inhaled formulations, including solid or aerosol, and by topical or other similar formulations. In addition to the appropriate therapeutic composition, such pharmaceutical compositions may contain pharmaceutically acceptable carriers and other ingredients known to enhance and facilitate drug administration. Other possible formulations, such as nanoparticles, liposomes, resealed erythrocytes, and immunologically based systems may also be used to administer an appropriate modulator thereof, according to the methods of the invention. The formulations of the pharmaceutical compositions described herein may be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of bringing the active ingredient into association with a carrier or one or more other accessory ingredients, and then, if necessary or desirable, shaping or packaging the product into a desired single- or multi-dose unit. Pharmaceutical compositions that are useful in the methods of the invention may be prepared, packaged, or sold in formulations suitable for oral, rectal, vaginal, parenteral, topical, pulmonary, intranasal, buccal, intravenous, ophthalmic, intrathecal and other known routes of administration. Other contemplated formulations include projected nanoparticles, liposomal preparations, resealed erythrocytes containing the active ingredient (e.g., a KRAS signaling or SFRP2 inhibitor), and immunologically- based formulations. A pharmaceutical composition of the invention may be prepared, packaged, or sold in bulk, as a single unit dose, or as a plurality of single unit doses. As used herein, a “unit dose” is discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage. The relative amounts of the active ingredient (e.g., the KRAS signaling or SFRP2 inhibitor), the pharmaceutically acceptable carrier, and any additional ingredients in a pharmaceutical composition of the invention will vary, depending upon the identity, size, and condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100% (w / w) active ingredient. In various embodiments, the composition comprises at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, at least about 67%, at least about 68%, at least about 69%, at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at least about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% (w / w) active ingredient. In addition to the active ingredient, a pharmaceutical composition of the invention may further comprise one or more additional pharmaceutically active agents. Controlled- or sustained-release formulations of a pharmaceutical composition of the invention may be made using conventional technology. A formulation of a pharmaceutical composition of the invention suitable for oral administration may be prepared, packaged, or sold in the form of a discrete solid dose unit including, but not limited to, a tablet, a hard or soft capsule, a cachet, a troche, or a lozenge, each containing a predetermined amount of the active ingredient. Other formulations suitable for oral administration include, but are not limited to, a powdered or granular formulation, an aqueous or oily suspension, an aqueous or oily solution, or an emulsion. A tablet comprising the active ingredient (e.g., a KRAS signaling or SFRP2 inhibitor) may, for example, be made by compressing or molding the active ingredient, optionally with one or more additional ingredients. Compressed tablets may be prepared by compressing, in a suitable device, the active ingredient in a free-flowing form such as a powder or granular preparation, optionally mixed with one or more of a binder, a lubricant, an excipient, a surface active agent, and a dispersing agent. Molded tablets may be made by molding, in a suitable device, a mixture of the active ingredient, a pharmaceutically acceptable carrier, and at least sufficient liquid to moisten the mixture. Pharmaceutically acceptable excipients used in the manufacture of tablets include, but are not limited to, inert diluents, granulating and disintegrating agents, binding agents, and lubricating agents. Known dispersing agents include, but are not limited to, potato starch and sodium starch glycolate. Known surface active agents include, but are not limited to, sodium lauryl sulphate. Known diluents include, but are not limited to, calcium carbonate, sodium carbonate, lactose, microcrystalline cellulose, calcium phosphate, calcium hydrogen phosphate, and sodium phosphate. Known granulating and disintegrating agents include, but are not limited to, corn starch and alginic acid. Known binding agents include, but are not limited to, gelatin, acacia, pre-gelatinized maize starch, polyvinylpyrrolidone, and hydroxypropyl methylcellulose. Known lubricating agents include, but are not limited to, magnesium stearate, stearic acid, silica, and talc. Tablets may be non-coated or they may be coated using known methods to achieve delayed disintegration in the gastrointestinal tract of a subject, thereby providing sustained release and absorption of the active ingredient. By way of example, a material such as glyceryl monostearate or glyceryl distearate may be used to coat tablets. Further by way of example, tablets may be coated using methods described in U.S. Pat. Nos. 4,256,108; 4,160,452; and 4,265,874 to form osmotically-controlled release tablets. Tablets may further comprise a sweetening agent, a flavoring agent, a coloring agent, a preservative, or some combination of these in order to provide pharmaceutically elegant and palatable preparation. Hard capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin. Such hard capsules comprise the active ingredient, and may further comprise additional ingredients including, for example, an inert solid diluent such as calcium carbonate, calcium phosphate, or kaolin. Soft gelatin capsules comprising the active ingredient may be made using a physiologically degradable composition, such as gelatin. Such soft capsules comprise the active ingredient, which may be mixed with water or an oil medium such as peanut oil, liquid paraffin, or olive oil. Liquid formulations of a pharmaceutical composition of the invention which are suitable for oral administration may be prepared, packaged, and sold either in liquid form or in the form of a dry product intended for reconstitution with water or another suitable vehicle prior to use. Liquid suspensions may be prepared using conventional methods to achieve suspension of the active ingredient in an aqueous or oily vehicle. Aqueous vehicles include, for example, water and isotonic saline. Oily vehicles include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. Liquid suspensions may further comprise one or more additional ingredients including, but not limited to, suspending agents, dispersing or wetting agents, emulsifying agents, demulcents, preservatives, buffers, salts, flavorings, coloring agents, and sweetening agents. Oily suspensions may further comprise a thickening agent. Known suspending agents include, but are not limited to, sorbitol syrup, hydrogenated edible fats, sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, and cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, and hydroxypropylmethylcellulose. Known dispersing or wetting agents include, but are not limited to, naturally-occurring phosphatides such as lecithin, condensation products of an alkylene oxide with a fatty acid, with a long chain aliphatic alcohol, with a partial ester derived from a fatty acid and a hexitol, or with a partial ester derived from a fatty acid and a hexitol anhydride (e.g. polyoxyethylene stearate, heptadecaethyleneoxycetanol, polyoxyethylene sorbitol monooleate, and polyoxyethylene sorbitan monooleate, respectively). Known emulsifying agents include, but are not limited to, lecithin and acacia. Known preservatives include, but are not limited to, methyl, ethyl, or n-propyl-para-hydroxybenzoates, ascorbic acid, and sorbic acid. Known sweetening agents include, for example, glycerol, propylene glycol, sorbitol, sucrose, and saccharin. Known thickening agents for oily suspensions include, for example, beeswax, hard paraffin, and cetyl alcohol. Liquid solutions of the active ingredient in aqueous or oily solvents may be prepared in substantially the same manner as liquid suspensions, the primary difference being that the active ingredient is dissolved, rather than suspended in the solvent. Liquid solutions of the pharmaceutical composition of the invention may comprise each of the components described with regard to liquid suspensions, it being understood that suspending agents will not necessarily aid dissolution of the active ingredient in the solvent. Aqueous solvents include, for example, water and isotonic saline. Oily solvents include, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin. Powdered and granular formulations of a pharmaceutical preparation of the invention may be prepared using known methods. Such formulations may be administered directly to a subject, used, for example, to form tablets, to fill capsules, or to prepare an aqueous or oily suspension or solution by addition of an aqueous or oily vehicle thereto. Each of these formulations may further comprise one or more of dispersing or wetting agent, a suspending agent, and a preservative. Additional excipients, such as fillers and sweetening, flavoring, or coloring agents, may also be included in these formulations. A pharmaceutical composition of the invention may also be prepared, packaged, or sold in the form of oil-in-water emulsion or a water-in-oil emulsion. The oily phase may be a vegetable oil such as olive or arachis oil, a mineral oil such as liquid paraffin, or a combination of these. Such compositions may further comprise one or more emulsifying agents such as naturally occurring gums such as gum acacia or gum tragacanth, naturally-occurring phosphatides such as soybean or lecithin phosphatide, esters or partial esters derived from combinations of fatty acids and hexitol anhydrides such as sorbitan monooleate, and condensation products of such partial esters with ethylene oxide such as polyoxyethylene sorbitan monooleate. These emulsions may also contain additional ingredients including, for example, sweetening or flavoring agents. Methods for impregnating or coating a material with a chemical composition are known in the art, and include, but are not limited to methods of depositing or binding a chemical composition onto a surface, methods of incorporating a chemical composition into the structure of a material during the synthesis of the material (i.e., such as with a physiologically degradable material), and methods of absorbing an aqueous or oily solution or suspension into an absorbent material, with or without subsequent drying. Parenteral administration of a pharmaceutical composition includes any route of administration characterized by physical breaching of a tissue of an individual and administration of the pharmaceutical composition through the breach in the tissue. Parental administration can be local, regional or systemic. Parenteral administration thus includes, but is not limited to, administration of a pharmaceutical composition by injection of the composition, by application of the composition through a surgical incision, by application of the composition through a tissue-penetrating non-surgical wound, and the like. In particular, parenteral administration is contemplated to include, but is not limited to, intravenous, intraocular, intravitreal, subcutaneous, intraperitoneal, intramuscular, intradermal, intrasternal injection, and intratumoral. Formulations of a pharmaceutical composition suitable for parenteral administration comprise the active ingredient combined with a pharmaceutically acceptable carrier, such as sterile water or sterile isotonic saline. Such formulations may be prepared, packaged, or sold in a form suitable for bolus administration or for continuous administration. Injectable formulations may be prepared, packaged, or sold in unit dosage form, such as in ampules or in multi-dose containers containing a preservative. Formulations for parenteral administration include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous vehicles, pastes, and implantable sustained-release or biodegradable formulations. Such formulations may further comprise one or more additional ingredients including, but not limited to, suspending, stabilizing, or dispersing agents. In some embodiments of a formulation for parenteral administration, the active ingredient is provided in dry (i.e., powder or granular) form for reconstitution with a suitable vehicle (e.g., sterile pyrogen-free water) prior to parenteral administration of the reconstituted composition. The pharmaceutical compositions may be prepared, packaged, or sold in the form of a sterile injectable aqueous or oily suspension or solution. This suspension or solution may be formulated according to the known art, and may comprise, in addition to the active ingredient, additional ingredients such as the dispersing agents, wetting agents, or suspending agents described herein. Such sterile injectable formulations may be prepared using a non-toxic parenterally-acceptable diluent or solvent, such as water or 1,3-butane diol, for example. Other acceptable diluents and solvents include, but are not limited to, Ringer’s solution, isotonic sodium chloride solution, and fixed oils such as synthetic mono- or di-glycerides. Other parentally-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form, in a liposomal preparation, or as a component of a biodegradable polymer systems. Compositions for sustained release or implantation may comprise pharmaceutically acceptable polymeric or hydrophobic materials such as an emulsion, an ion exchange resin, a sparingly soluble polymer, or a sparingly soluble salt. Formulations suitable for topical administration include, but are not limited to, liquid or semi-liquid preparations such as liniments, lotions, oil-in-water or water-in-oil emulsions such as creams, ointments or pastes, and solutions or suspensions. Topically-administrable formulations may, for example, comprise from about 1% to about 10% (w / w) active ingredient, although the concentration of the active ingredient may be as high as the solubility limit of the active ingredient in the solvent Formulations for topical administration may further comprise one or more of the additional ingredients described herein. A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for pulmonary administration via the buccal cavity. Such a formulation may comprise dry particles which comprise the active ingredient and which have a diameter in the range from about 0.5 to about 7 nanometers, and preferably from about 1 to about 6 nanometers. Such compositions are conveniently in the form of dry powders for administration using a device comprising a dry powder reservoir to which a stream of propellant may be directed to disperse the powder or using a self-propelling solvent / powder-dispensing container such as a device comprising the active ingredient dissolved or suspended in a low-boiling propellant in a sealed container. Preferably, such powders comprise particles wherein at least 98% of the particles by weight have a diameter greater than 0.5 nanometers and at least 95% of the particles by number have a diameter less than 7 nanometers. More preferably, at least 95% of the particles by weight have a diameter greater than 1 nanometer and at least 90% of the particles by number have a diameter less than 6 nanometers. In some embodiments, dry powder compositions include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form. Low boiling propellants generally include liquid propellants having a boiling point of below 65 °F at atmospheric pressure. Generally, the propellant may constitute 50 to 99.9% (w / w) of the composition, and the active ingredient may constitute 0.1 to 20% (w / w) of the composition. The propellant may further comprise additional ingredients such as a liquid non-ionic or solid anionic surfactant or a solid diluent (in some embodiments having a particle size of the same order as particles comprising the active ingredient). Pharmaceutical compositions of the invention formulated for pulmonary delivery may also provide the active ingredient in the form of droplets of a solution or suspension. Such formulations may be prepared, packaged, or sold as aqueous or dilute alcoholic solutions or suspensions, optionally sterile, comprising the active ingredient, and may conveniently be administered using any nebulization or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, or a preservative such as methylhydroxybenzoate. The droplets provided by this route of administration preferably have an average diameter in the range from about 0.1 to about 200 nanometers. The formulations described herein as being useful for pulmonary delivery are also useful for intranasal delivery of a pharmaceutical composition of the invention. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 to 500 micrometers. Such a formulation is administered in the manner in which snuff is taken i.e. by rapid inhalation through the nasal passage from a container of the powder held close to the nares. Formulations suitable for nasal administration may, for example, comprise from about as little as 0.1% (w / w) and as much as 100% (w / w) of the active ingredient, and may further comprise one or more of the additional ingredients described herein. A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets or lozenges made using conventional methods, and may, for example, contain 0.1 to 20% (w / w) active ingredient, the balance comprising an orally dissolvable or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise a powder or an aerosolized or atomized solution or suspension comprising the active ingredient. Such powdered, aerosolized, or aerosolized formulations, when dispersed, preferably have an average particle or droplet size in the range from about 0.1 nanomaters to about 2000 micrometers, and may further comprise one or more of the additional ingredients described herein. A pharmaceutical composition of the invention may be prepared, packaged, or sold in a formulation suitable for ophthalmic administration. Such formulations may, for example, be in the form of eye drops including, for example, a 0.1- 1.0% (w / w) solution or suspension of the active ingredient in an aqueous or oily liquid carrier. Such drops may further comprise buffering agents, salts, or one or more other of the additional ingredients described herein. Other opthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form or in a liposomal preparation. As used herein, “additional ingredients” include, but are not limited to, one or more of the following: excipients; surface active agents; dispersing agents; inert diluents; granulating and disintegrating agents; binding agents; lubricating agents; sweetening agents; flavoring agents; coloring agents; preservatives; physiologically degradable compositions such as gelatin; aqueous vehicles and solvents; oily vehicles and solvents; suspending agents; dispersing or wetting agents; emulsifying agents, demulcents; buffers; salts; thickening agents; fillers; emulsifying agents; antioxidants; antibiotics; antifungal agents; stabilizing agents; and pharmaceutically acceptable polymeric or hydrophobic materials. Other “additional ingredients” which may be included in the pharmaceutical compositions of the invention are known in the art and described, for example in Genaro, ed., 1985, Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa. Administration of the compounds of the present invention or the compositions thereof may be continuous or intermittent, depending, for example, upon the recipient’s physiological condition, whether the purpose of the administration is therapeutic or prophylactic, and other factors known to skilled practitioners. The administration of the agents of the invention may be essentially continuous over a preselected period of time or may be in a series of spaced doses. Both local and systemic administration is contemplated. The amount administered will vary depending on various factors including, but not limited to, the composition chosen, the particular disease, the weight, the physical condition, and the age of the mammal, and whether prevention or treatment is to be achieved. Such factors can be readily determined by the clinician employing animal models or other test systems which are well known to the art. One or more suitable unit dosage forms having the therapeutic agent(s) of the invention, which, as discussed below, may optionally be formulated for sustained release (for example using microencapsulation, see WO 94 / 07529, and U.S. Pat. No. 4,962,091 the disclosures of which are incorporated by reference herein), can be administered by a variety of routes including parenteral, including by intravenous and intramuscular routes, as well as by direct injection into the diseased tissue. For example, the therapeutic agent may be directly injected into the muscle. The formulations may, where appropriate, be conveniently presented in discrete unit dosage forms and may be prepared by any of the methods well known to pharmacy. Such methods may include the step of bringing into association the therapeutic agent with liquid carriers, solid matrices, semi-solid carriers, finely divided solid carriers or combinations thereof, and then, if necessary, introducing or shaping the product into the desired delivery system. When the therapeutic agents of the invention are prepared for administration, they are preferably combined with a pharmaceutically acceptable carrier, diluent or excipient to form a pharmaceutical formulation, or unit dosage form. The total active ingredients in such formulations include from 0.1 to 99.9% by weight of the formulation. A “pharmaceutically acceptable” is a carrier, diluent, excipient, and / or salt that is compatible with the other ingredients of the formulation, and not deleterious to the recipient thereof. The active ingredient for administration may be present as a powder or as granules; as a solution, a suspension or an emulsion. Pharmaceutical formulations containing the therapeutic agents of the invention can be prepared by procedures known in the art using well known and readily available ingredients. The therapeutic agents of the invention can also be formulated as solutions appropriate for parenteral administration, for instance by intramuscular, subcutaneous or intravenous routes. The pharmaceutical formulations of the therapeutic agents of the invention can also take the form of an aqueous or anhydrous solution or dispersion, or alternatively the form of an emulsion or suspension. Thus, the therapeutic agent may be formulated for parenteral administration (e.g., by injection, for example, bolus injection or continuous infusion) and may be presented in unit dose form in ampules, pre-filled syringes, small volume infusion containers or in multi-dose containers with an added preservative. The active ingredients may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Alternatively, the active ingredients may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use. It will be appreciated that the unit content of active ingredient or ingredients contained in an individual aerosol dose of each dosage form need not in itself constitute an effective amount for treating the particular indication or disease since the necessary effective amount can be reached by administration of a plurality of dosage units. Moreover, the effective amount may be achieved using less than the dose in the dosage form, either individually, or in a series of administrations. The pharmaceutical formulations of the present invention may include, as optional ingredients, pharmaceutically acceptable carriers, diluents, solubilizing or emulsifying agents, and salts of the type that are well-known in the art. Specific non- limiting examples of the carriers and / or diluents that are useful in the pharmaceutical formulations of the present invention include water and physiologically acceptable buffered saline solutions, such as phosphate buffered saline solutions pH 7.0-8.0. In general, water, suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration contain the active ingredient, suitable stabilizing agents and, if necessary, buffer substances. Antioxidizing agents such as sodium bisulfate, sodium sulfite or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium Ethylenediaminetetraacetic acid (EDTA). In addition, parenteral solutions can contain preservatives such as benzalkonium chloride, methyl or propyl-paraben and chlorobutanol. Suitable pharmaceutical carriers are described in Remington’s Pharmaceutical Sciences, a standard reference text in this field. The active ingredients of the invention may be formulated to be suspended in a pharmaceutically acceptable composition suitable for use in mammals and in particular, in humans. Such formulations include the use of adjuvants such as muramyl dipeptide derivatives (MDP) or analogs that are described in U.S. Patent Nos.4,082,735; 4,082,736; 4,101,536; 4,185,089; 4,235,771; and 4,406,890. Other adjuvants, which are useful, include alum (Pierce Chemical Co.), lipid A, trehalose dimycolate and dimethyldioctadecylammonium bromide (DDA), Freund’s adjuvant, and IL 12. Other components may include a polyoxypropylene-polyoxyethylene block polymer (Pluronic®), a non-ionic surfactant, and a metabolizable oil such as squalene (U.S. Patent No.4,606,918). Additionally, standard pharmaceutical methods can be employed to control the duration of action. These are well known in the art and include control release preparations and can include appropriate macromolecules, for example polymers, polyesters, polyamino acids, polyvinyl, pyrolidone, ethylenevinylacetate, methyl cellulose, carboxymethyl cellulose or protamine sulfate. The concentration of macromolecules as well as the methods of incorporation can be adjusted in order to control release. Additionally, the agent can be incorporated into particles of polymeric materials such as polyesters, polyamino acids, hydrogels, poly (lactic acid) or ethylenevinylacetate copolymers. In addition to being incorporated, these agents can also be used to trap the compound in microcapsules. Accordingly, the composition of the present invention may be delivered via various routes and to various sites in a mammal body to achieve a particular effect (see, e.g., Rosenfeld et al., 1991; Rosenfeld et al., 1991a; Jaffe et al., supra; Berkner, supra). One skilled in the art will recognize that although more than one route can be used for administration, a particular route can provide a more immediate and more effective reaction than another route. In some embodiments, the composition described above is administered to the subject by subretinal injection. In other embodiments, the composition is administered by intravitreal injection. Other forms of administration that may be useful in the methods described herein include, but are not limited to, direct delivery to a desired organ (e.g., the eye), oral, inhalation, intranasal, intratracheal, intravenous, intramuscular, subcutaneous, intradermal, and other parental routes of administration. Additionally, routes of administration may be combined, if desired. In another embodiments, route of administration is subretinal injection or intravitreal injection. The active ingredients of the present invention can be provided in unit dosage form wherein each dosage unit, e.g., a teaspoonful, tablet, solution, or suppository, contains a predetermined amount of the composition, alone or in appropriate combination with other active agents. The term “unit dosage form” as used herein refers to physically discrete units suitable as unitary dosages for human and mammal subjects, each unit containing a predetermined quantity of the compositions of the present invention, alone or in combination with other active agents, calculated in an amount sufficient to produce the desired effect, in association with a pharmaceutically acceptable diluent, carrier, or vehicle, where appropriate. The specifications for the unit dosage forms of the present invention depend on the particular effect to be achieved and the particular pharmacodynamics associated with the composition in the particular host. The pharmaceutical compositions useful for practicing the invention may be administered to deliver a dose of at least about 1 ng / kg, at least about 5 ng / kg, at least about 10 ng / kg, at least about 25 ng / kg, at least about 50 ng / kg, at least about 100 ng / kg, at least about 500 ng / kg, at least about 1 µg / kg, at least about 5 µg / kg, at least about 10 µg / kg, at least about 25 µg / kg, at least about 50 µg / kg, at least about 100 µg / kg, at least about 500 µg / kg, at least about 1 mg / kg, at least about 5 mg / kg, at least about 10 mg / kg, at least about 25 mg / kg, at least about 50 mg / kg, at least about 100 mg / kg, at least about 200 mg / kg, at least about 300 mg / kg, at least about 400 mg / kg, and at least about 500 mg / kg of body weight of the subject. In some embodiments, the pharmaceutical compositions useful for practicing the invention may be administered to deliver a dose of no more than about 1 ng / kg, no more than about 5 ng / kg, no more than about 10 ng / kg, no more than about 25 ng / kg, no more than about 50 ng / kg, no more than about 100 ng / kg, no more than about 500 ng / kg, no more than about 1 µg / kg, no more than about 5 µg / kg, no more than about 10 µg / kg, no more than about 25 µg / kg, no more than about 50 µg / kg, no more than about 100 µg / kg, no more than about 500 µg / kg, no more than about 1 mg / kg, no more than about 5 mg / kg, no more than about 10 mg / kg, no more than about 25 mg / kg, no more than about 50 mg / kg, no more than about 100 mg / kg, no more than about 200 mg / kg, no more than about 300 mg / kg, no more than about 400 mg / kg, and no more than about 500 mg / kg of body weight of the subject. Also contemplated are dosage ranges between any of the doses disclosed herein. Typically, dosages which may be administered in a method of the invention to a subject, in some embodiments a human, range in amount from 0.5 μg to about 100 g per kilogram of body weight of the subject. While the precise dosage administered will vary depending upon any number of factors, including but not limited to, the type of subject and type of disease state being treated, the age of the subject and the route of administration. In some embodiments, the dosage of the compound will vary from about 1 μg to about 10 mg per kilogram of body weight of the subject. In other embodiments, the dosage will vary from about 3 μg to about 1 mg per kilogram of body weight of the subject. The compositions may be administered to a subject as frequently as several times daily, or it may be administered less frequently, such as once a day, twice a day, thrice a day, once a week, twice a week, thrice a week, once every two weeks, twice every two weeks, thrice every two weeks, once a month, twice a month, thrice a month, or even less frequently, such as once every several months or even once or a few times a year or less. The frequency of the dose will be readily apparent to the skilled artisan and will depend upon any number of factors, such as, but not limited to, the type and severity of the disease being treated, the type and age of the subject, etc. The formulations of the pharmaceutical compositions may be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of bringing the active ingredient into association with a carrier or one or more other accessory ingredients, and then, if necessary or desirable, shaping or packaging the product into a desired single- or multi-dose unit. Individuals to which administration of the pharmaceutical compositions of the invention is contemplated include, but are not limited to, humans and other primates, mammals including commercially relevant mammals such as non-human primates, cattle, pigs, horses, sheep, cats, and dogs. These compositions described herein are by no means all inclusive, and further modifications to suit the specific application will be apparent to the ordinary skilled artisan. Moreover, the effective amount of the compositions can be further approximated through analogy to compounds known to exert the desired effect. Kits The present invention also pertains to kits useful in the methods of the invention. Such kits comprise various combinations of components useful in any of the methods described elsewhere herein, including for example, materials for inhibiting KRAS signaling or SFRP2, quantitatively analyzing KRAS signaling or the level or activity of SFRP2, materials for diagnosing or assessing the prognosis of a disease or disorder associated with KRAS signaling or SFRP2, materials for preventing or treating a disease or disorder associated with KRAS signaling or SFRP2, materials for monitoring a treatment, and instructional material. For example, in one embodiment, the kit comprises components useful for analyzing KRAS signaling or the level or activity of SFRP2 in a biological sample. In a further embodiment, the kit comprises components useful for diagnosing or assessing the prognosis of a disease or disorder associated with KRAS signaling or the level or activity of SFRP2. In a further embodiment, the kit comprises components useful for inhibiting KRAS signaling or SFRP2. In a further embodiment, the kit comprises components useful for preventing or treating a disease or disorder associated with KRAS signaling or the level or activity of SFRP2. In a further embodiment, the kit comprises the components of an assay for monitoring the effectiveness of a treatment administered to a subject in need thereof, containing instructional material and the components for determining whether the level of KRAS signaling or SFRP2 in a biological sample obtained from the subject is modulated during or after administration of the treatment. In various embodiments, to determine whether the level of KRAS signaling or SFRP2 is modulated in a biological sample obtained from the subject, the level of KRAS signaling or SFRP2 is compared with the level of at least one comparator contained in the kit, such as a positive control, a negative control, a historical control, a historical norm, or the level of another reference molecule. In certain embodiments, the ratio of KRAS signaling or SFRP2 and a reference molecule is determined to aid in the monitoring of the treatment. EXEMPLARY EMBODIMENTS This invention provides the following non-limiting embodiments. Embodiment 1 is a method of treating or preventing a disease or disorder in a subject, the method comprising: a) detecting the level of Kirsten rat sarcoma viral oncogene homologue (KRAS) signaling in a sample; b) comparing the level of KRAS signaling to the level in a comparator control; c) diagnosing the subject as having or at risk of developing a disease or disorder when the level of KRAS signaling is increased as compared to the comparator control; and d) administering to the subject an inhibitor of SFRP2 for the treatment or prevention of the diagnosed disease or disorder. Embodiment 2 is method of embodiment 1, wherein the inhibitor of SFRP2 comprises an anti- SFRP2 antibody comprising a complementary determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:19, a CDR H2 comprising the amino acid sequence of SEQ ID NO:20, a CDR H3 comprising the amino acid sequence of SEQ ID NO:21, a CDR LI comprising the amino acid sequence of SEQ ID NO:22, a CDR L2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:24. Embodiment 3 is method of embodiment 1 or 2, wherein the comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level of KRAS signaling in a control population. Embodiment 4 is method of any one of embodiments 1 through 3, wherein the disease or disorder is pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer. Embodiment 5 is method of any one of embodiments 1 through 4, wherein the disease or disorder is pancreatic adenocarcinoma. Embodiment 6 is method of any one of embodiments 1 through 4, wherein the disease or disorder is lung cancer. Embodiment 7 is the method of any one of embodiments 1 through 6, wherein the subject is human. Embodiment 8 is a method of diagnosing a subject with a disease or disorder, the method comprising: a) detecting the level or activity of secreted frizzled- related protein 2 (SFRP2) in a sample, comparing the level or activity of SFRP2 to the level in a first comparator control, b) detecting the level of Kirsten rat sarcoma viral oncogene homologue (KRAS) or KRAS signaling in a sample, comparing the level of KRAS or KRAS signaling to the level in a second comparator control, and c) diagnosing the subject as having or at risk of developing a disease or disorder when the level or activity of the combination of SFRP2 and KRAS or KRAS signaling is increased as compared to the comparator control. Embodiment 9 is the method of embodiment 8, wherein the first comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level or activity of SFRP2 in a control population, and the second comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level of KRAS or KRAS signaling in a control population. Embodiment 10 is the method of embodiment 8 or 9, wherein the disease or disorder is pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer. Embodiment 11 is the method of any one of embodiments 8 through 10, wherein the disease or disorder is pancreatic adenocarcinoma. Embodiment 12 is the method of any one of embodiments 8 through 10, wherein the disease or disorder is lung cancer. Embodiment 13 is a method of treating or preventing a disease or disorder in a subject, the method comprising the method of any one of embodiments 8 through 12, further comprising administering to the subject a composition for the treatment or prevention of the diagnosed disease or disorder. Embodiment 14 is the method of embodiment 13, wherein the composition comprises an inhibitor of SFRP2, an inhibitor of KRAS signaling or a combination thereof. Embodiment 15 is the method of embodiment 13 or 14, wherein the inhibitor comprises a chemical compound, a protein, a peptide, a peptidomimetic, an antibody, an antibody fragment, an antibody mimetic, a chimeric antibody, a bispecific antibody, a ribozyme, a small molecule chemical compound, a short hairpin RNA, RNAi, siRNA, miRNA, or a nucleic acid encoding an antisense nucleic acid molecule. Embodiment 16 is the method of any one of embodiments 13 through 15, wherein the method comprises administering a combination of a) Sotorasib, adagrasib or MRTX1133 and b) an anti-SFRP2 antibody. Embodiment 17 is the method of any one of embodiments 13 through 16, wherein the inhibitor of SFRP2 comprises an anti-SFRP2 antibody comprising a complementary determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:19, a CDR H2 comprising the amino acid sequence of SEQ ID NO:20, a CDR H3 comprising the amino acid sequence of SEQ ID NO:21, a CDR LI comprising the amino acid sequence of SEQ ID NO:22, a CDR L2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:24. Embodiment 18 is the method of any one of embodiments 13 through 17, further comprising the step of administering to the subject at least one additional therapeutic or prophylactic agent. Embodiment 19 is the method of any one of embodiments 13 through 18, wherein the disease or disorder is at least one selected from the group consisting of pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer. Embodiment 20 is the method of any one of embodiments 13 through 19, wherein the disease or disorder is pancreatic adenocarcinoma. Embodiment 21 is the method of any one of embodiments 13 through 19, wherein the disease or disorder is lung cancer. Embodiment 22 is the method of any one of embodiments 13 through 21, wherein the subject is human. EXPERIMENTAL EXAMPLES The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working examples therefore are not to be construed as limiting in any way the remainder of the disclosure. Example 1: Secreted frizzled related-protein 2 is prognostic for human pancreatic cancer patient survival and is associated with fibrosis Pancreatic adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates of 9%. Without being bound by theory, it was examined whether secreted frizzled-related protein 2 (SFRP2) may influence stromal growth in pancreatic cancer, since it increases fibrosis and collagen production in non-neoplastic pathologies. This study assessed SFRP2 value as a biomarker and assessed its function in PDAC. SFRP2 gene expression in patients with PDAC were analyzed using TCGA data. Disease free survival (DFS) was analyzed using Kaplan Meier test. The effect of KRAS inhibition on SFRP2 expression in PDAC cells was assessed. The associations of stromal content with SFPR2 mRNA and protein with fibrosis were analyzed. The role of SFRP2 in mesenchymal transformation was assessed by western blot in fibroblasts. Of all cancers in TCGA, SFRP2 levels were highest in PDAC, and higher in PDAC than normal tissues (n=234, p=0.0003). High SFRP2 levels correlated with decreased DFS (p=0.0097). KRAS inhibition reduced SFRP2 levels. Spearman correlation was 0.81 between stromal RNA and SFRP2 in human PDAC, and 0.75 between fibrosis and SFRP2 levels in PDAC tumors. SFRP2-treated fibroblasts displayed mesenchymal characteristics. SFRP2 is prognostic for PDAC survival, regulated by KRAS, and associated with PDAC fibrosis. This study sought to explore the relationship between SFRP2 and pancreatic cancer to determine whether SFRP2 expression is associated with survival and tumor fibrosis, and whether it is regulated by KRAS, a major driver of PDAC. Additionally, this study investigated the ability of SFRP2 to promote the mesenchymal transformation of fibroblasts and stimulation of fibrinogen production. The materials and methods used in these experiments are now described. Cell lines, cell isolation, and tissue culture Pancreatic cancer cell lines AsPC-1, MIA PaCa-2, and Panc02-luc were obtained. Panc02-luc were originally obtained from the NCI DCTD Tumor Repository and transfected as previously described (E.C. Little et al., J Surg Res 176 (2012), 359- 66). AsPC-1 and MIA PaCA-2 were from American Type Culture Collection (ATCC CRL-1420). PANC-1R15and PSN-1R15cells were generated as previously described (I. Khan et al., Cell Reports (2022) 38(6):110322). Primary human skin fibroblasts (C.A. Feghali and T.M. Wright, Arthritis Rheum 42 (1999), 1451-7) were obtained. The mouse angiosarcoma cell line, SVR (J.L. Arbiser et al., Proc Natl.Acad.Sci.U.S.A 94 (1997), 861-866) was purchased from ATCC (#CRL-2280). A male C57 / BL6NCrl mouse purchased from Charles River Laboratory (Wilmington, MA) was used to isolate pancreatic fibroblasts. The pancreas was resected after euthanasia and was washed with ice- cold modified Krebs-Hensleit buffer supplemented with 2.1 g / L sodium bicarbonate (pH 7.4). Next, 1 mL of ice-cold digestion mix (34.4 mL Hanks buffered saline solution (HBSS; #55037C-1000 mL, Sigma-Aldrich, St. Louis, MO, USA), 1mL Liberase mix (5 mg in 2 mL of HBSS; # 541020001, Roche, Basel, Switzerland), 200 mL 0.25% Trypsin (# 25-050-CL, Corning, Corning, NY, USA), 360 mL 1M HEPES buffer (#H4034-25G, Sigma-Aldrich) was added, and tissue was macerated using a razor blade. The macerated tissue and digestion mix was placed into a 15 mL falcon tube, and an additional 3 mL of digestion mix at 37ºC was added. The mix was incubated on a tube rotator at 37ºC for 8 min.10 mL of modified Krebs-Hensleit buffer containing 2.1 g / L sodium bicarbonate (#K3753, Sigma- Aldrich) was added to quench the digestion, and the mixture was briefly rested to allow the tissue chunks to collect at the bottom. The supernatant containing the cellular suspension was removed and placed on ice. Digestion mix (3 mL at 37ºC) was added and another round of incubation on the tube rotator was performed for 8 min. Once again, the supernatant was placed on ice, and the digestion was repeated until no visible chunks of tissue remained in the tube. The supernatants were then combined in a 50 mL falcon tube, centrifuged for 5 min at 1200 rpm, and washed with 10 mL Krebs-Hensleit buffer and centrifuged again at 1200 rpm for 5 min. Each pellet was finally resuspended in Human Cardiac Fibroblast growth media (#316-500, Cell Applications, San Diego, CA, USA) containing 1% penicillin / streptomycin (#15140122, Thermofisher, Waltham, MA, USA), placed into a 10 cm Petri dish, and grown to confluence. SVR angiosarcoma, pancreatic cancer MIA PaCA-2 cell line, human skin fibroblasts, and mouse pancreatic fibroblasts were cultured in Dulbecco's Modified Eagle Medium (DMEM, #10-013-CV, Corning) with 10% fetal bovine serum (FBS) (#BT 201- 500-D, BioFluid, Fleming Island, FL, USA). AsPC-1 and Panc02-luc pancreatic cancer cell lines were cultured in Roswell Park Memorial Institute (RPMI) media with 10% FBS. All cell lines were cultured at 37°C, 5% CO2, and 95% humidity. In vivo pancreatic cancer GEMM mouse model KPC male and female mice (Krastm4TyjTrp53tm1BrnTg(Pdx1- cre / Esr1*)#Dam / J) (n=8) were obtained at 4-8 weeks of age from Jackson Laboratories (Bar Harbor, ME, USA). The sex distribution of more females than males was based on the availability of mice from the vendor. KPC mice are a genetically engineered mouse model (GEMM) with conditionally silenced p53 and KRAS mutations that are activated by a Cre recombinase enzyme bound to a mutant estrogen receptor ligand binding domain. Tamoxifen induces Cre recombinase expression, which results in the development of pancreatic intraepithelial neoplasia and eventually PDAC with 100% penetrance (A. Gopinathan et al., Dis Model Mech 8 (2015), 1185-200). Since animals were provided based on availability, there were seven females and one male. Mice were only housed together if they were littermates. At eight-weeks of age, mice received 100 µL IP injections of tamoxifen 100 mg / kg (#T5648, Sigma-Aldrich) resuspended in corn oil. Pancreatic tumors were resected at end point (age range 4-9 months). Tumors were fixed in formalin and embedded in paraffin. Mice were never fasted and received Harlan Teklad Irradiated 2918 diet, standard water, and were housed in vent-rack caging. Antibodies and proteins Primary antibodies used included rabbit anti-actin (#A2103, Sigma- Aldrich), mouse anti-fibronectin (#610077, BD Biosciences, Franklin Lakes, NJ, USA), rabbit anti-frizzled-5 (H00007855-PW1, Abnova, Taipei, Taiwan), rabbit anti-GAPDH (glyceraldehyde-3-phosphate dehydrogenase, #ab9485, Abcam, Cambridge, MA, USA), rabbit anti-N-cadherin (#ab1221, Abcam), mouse anti-Vinculin (SC #73614, Santa Cruz Biotechnology, Dallas, TX, USA). Rabbit anti-Vinculin (E1E9V) (#13901, Cell Signaling Technologies, Danvers, Massachusetts, USA), Phospho-p44 / 42 MAPK (Erk1 / 2) (Thr202 / Tyr204) Antibody (#9101, Cell Signaling Technologies, Danvers, Massachusetts, USA), p44 / 42 MAPK (Erk1 / 2) Antibody (#9102, Cell Signaling Technologies, Danvers, Massachusetts, USA). Rabbit anti-SFRP2 (#ab86379, Abcam), rabbit anti- SFRP2 (#ab137560 Abcam), and rabbit anti-SFRP2 (#LS-C61791, Lifespan Biosciences, Seattle, Washington, USA) were purchased based on manufacturers’ availability. Secondary antibodies used were biotinylated- conjugated anti-rabbit (#BA- 1000, Vector Laboratories, Burlingame, CA, USA), horse-radish peroxidase (HRP)- conjugated anti-mouse (#7076, Cell Signaling, Danvers, MA, USA), HRP-conjugated anti-rabbit (#403005, Southern Biotech, Birmingham, AL, USA), and Goat Anti-Rabbit IgG-HRP (#4030-50, Southern Biotech, Birmingham, AL, USA). Recombinant human SFRP2 protein (SFRP2) was prepared as previously described (Y.K. Peterson et al., Angiogenesis 20 (2017), 615-628), and provided by the Protein Expression and Purification Core facility from the University of North Carolina, Chapel Hill. SFRP2 mRNA expression SFRP2 mRNA expression levels were determined using the Cancer Genome Atlas (TCGA) database that was accessed on cBioPortal (E. Cerami et al., Cancer Discov 2 (2012), 401-4; J. Gao et al., Sci Signal 6 (2013), pl1). On cBioPortal, the SFRP2 gene was queried for all cancer types in the TCGA database. SFRP2 mRNA expression levels were collected for each patient and each cancer type, and descriptive statistics were performed. Gene Expression Profiling Interactive Analysis (GEPIA) (Z. Tang et al., Nucleic Acids Res 45 (2017), W98-W102) is an online tool that includes RNA sequencing data from several databases and can be used for interactive analysis of differential gene expression, profile plotting, survival analysis, and correlation analysis. GEPIA was used to analyze the differential RNA expression of SFRP2 in pancreatic cancer in the TCGA compared to normal pancreatic tissue. Survival analysis with the Kaplan-Meier method was also conducted through GEPIA to determine the association of disease-free survival with high or low RNA expression of SFRP2 in TCGA samples. Publicly available datasets were observed to explore percentiles at which there was a statistically significant decrement in survival. Based on these mRNA data, the cutoffs that can be used are the 20th percentile or less for low group and 50th percentile or greater for the high group provided a statistical separation of survival. SFRP2 mRNA expression correlation to stroma in pancreatic cancer The level of SFRP2 mRNA expression in pancreatic cancer was obtained in units of fragments per kilobase of transcript per million (FPKM) from the Human Protein Atlas (proteinatlas.org / about / download) (M. Uhlen et al., Science 357 (2017). The level of stromal content for each of these samples was evaluated with the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) provided by the MD Anderson Cancer Center (ESTIMATE: Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data). This scoring uses the TCGA mRNA data to analyze the stromal cell presence in the tumor and the immune cell infiltration. The stromal score was obtained using ESTIMATE, which measures the level of stroma in tumor tissue, and a Spearman correlation between the stromal score and SFRP2 mRNA expression levels for these patient samples was conducted. Protein extraction from pancreatic tumor tissues Human pancreatic tumor samples and their matched normal adjacent tissues from pancreatic resections were obtained. These de- identified tissues were obtained from institutional surgical specimens and were stored at -80ºC prior to use. Samples were crushed in liquid nitrogen into a fine powder, and 30-100 mg were mixed in Radioimmunoprecipitation assay, or RIPA, buffer (#R3792; TEKnova, Hollister, CA, USA), for protein lysis. Lysates were sonicated, centrifuged at 13,000 g, and supernatants were collected. Lysates were dialyzed, and then additional RIPA buffer was added. Immunohistochemistry Pancreatic tumors were resected from KPC mice, fixed in formalin, paraffin-embedded, and 8 µm thick slices were sectioned. Slides were deparaffinized, rehydrated, and antigen retrieval was performed using heat-mediated, citrate-based Antigen Unmasking Solution (#3300-250, Vector Laboratories) for 30 min. Endogenous peroxidases were blocked with hydrogen peroxide at a concentration of 1:100 (#5155-01, J.T. Baker, Phillipsburg, NJ, USA). Normal goat serum (#50062Z, Thermofisher) was used for non-specific protein blocking. Slides were incubated with the primary antibody (anti-SFRP2 #LS-C61791, Lifespan Biosciences, 1:50), and a negative control was performed with no primary antibody for 90 min at room temperature (RT). Slides were subsequently incubated with the secondary antibody (biotinylated anti- rabbit, 1:150) for 30 min at RT, followed by a 30 min incubation with Vectastain (PK-4000, Vector Laboratories), and an incubation with DAB (#1856090, Thermofisher) followed by a hematoxylin counterstaining (#H3401, Vector Laboratories). Masson Trichrome staining was performed with the Masson Trichome Staining kit (#84000-286, VWR International, Radnor, PA, USA). Slides were incubated in Bouin solution for 1 hour at 56ºC. Slides were consecutively stained with fresh Weigert’s hematoxylin for 10 min, Biebrich Scarlet – Acid Fuchsin Solution for 5 min, and then incubated in phosphmolybdic- phosphotungstic acid solution for 10 min. Tissues were then stained with Aniline Blue solution for 5 min, differentiated in acetic acid solution for 1 minute, dehydrated, and cleared with xylene. Picrosirius red staining was performed by incubating slides for 1 hour in picrosirius red solution containing picric acid (#101410-760, VWR International) and Sirius Red F3B (#43665, Sigma-Aldrich). Slides were washed with two changes of acetic acid solution, then dehydrated and cleared. The pancreatic tumors were ranked by their degree of fibrosis after interpretation of the Masson trichome staining and picrosirius red staining by a veterinarian pathologist (K.H.). The SFRP2 staining intensity in tumor cells and percentage of positive tumor cells were scored by a pathologist (L.S.). Each tumor was then ranked by level of SFRP2 staining. These rankings for fibrosis and SFRP2 staining were used to calculate the Spearman correlation coefficient. Evaluation of epithelial mesenchymal transformation in fibroblasts Mouse pancreatic fibroblasts and human skin fibroblasts were plated at 60% confluence in DMEM with 10% FBS and treated with either TGFβ at 5 nM, SFRP recombinant protein (SFRP2) at 30 nM, or no treatment. At 48 hours, fibroblasts were removed from the plate, washed twice with PBS, and centrifuged at 500 g for 5 min. Fibroblasts were lysed with RIPA buffer, kept on ice for 15 min, and sonicated. Effect of KRAS Inhibition on SFRP2 Expression in PDAC Cells PANC-1R15and PSN-1R15were treated with doxycycline (DOX) to induce expression of R15 Monobody, which selectively inhibits a subset of oncogenic KRAS proteins including KRASG12Dand KRASG12R(I. Khan et al., Cell Reports (2022) 38(6):110322). Following DOX treatment (1-2 µg / mL for 2 days), cells were lysed and then examined for SFRP2 expression by western blot analysis. Previous results confirmed inhibition of the ERK-MAPK pathway in these cells (I. Khan et al., Cell Reports (2022) 38(6):110322). Additionally, lysates from a xenograft tumor arising from injection of PANC-1R15cells in the flanks of athymic nude mice treated with (+) or without (-) DOX were also examined. To determine if KRAS inhibition alters SFRP2 expression, KRAS activity was inhibited by a second method using a KRASG12Dinhibitor, MRTX1133 (Selleckchem, E1051, Houston, TX) (X. Wang et al., J Med Chem 65 (2022), 3123- 3133), on PANC-1 pancreatic cancer cells and performing western blot probing for SFRP2. In this experiment, PANC-1 cells were treated with MRTX1133 (20 µM from 4 to 48 hours, or 10 µM for 24 and 48 hours). Negative controls included media alone for the initial time point and 20 nM DMSO (#D2650) for the 48-hour time point (Sigma, St. Louis, MO, USA). When the 4-hour timepoint required to visualize the maximum effects of KRAS inhibition on SFRP2 expression was established, a second cell line, MIA PaCa- 2, was tested to confirm the involvement of KRAS signaling through the RAF / MEK and PI3K pathway in SFRP2 regulation. Cells were treated with the B-RAF inhibitor, dabrafenib, at 0.1 µM (Selleckchem, 1195768-06-9), the MEK inhibitor, trametinib, at 100 nM (Selleckchem, 1187431-43-1), or the PI3K inhibitor, buparlisib, at 1 µM (Selleckchem, 944396-07-0) for 4 hours. Cells were then lysed and probed for Phospho- ERK, ERK, and SFRP2 using western blot analysis. Western blot analysis The protein content was equalized across samples using a Bradford solution, Bio-Rad Protein Assay (#500-0205, Bio-Rad Laboratories). Samples containing equal amounts of total protein were run on 10% bis-tris SDS-PAGE gels (#NW00100BOX Invitrogen) for 1 hour at 140V. Proteins were transferred onto a PVDF membrane (#LC2005 Life Technologies; Carlsbad, CA, USA) at 30V for 70 min. Membranes were then incubated for 30 min at RT in blocking buffer (PBS, Twin 0.1%, 5% milk), and then at 4 °C overnight with the primary antibody resuspended in blocking buffer. The following day, membranes were incubated with a HRP-conjugated secondary antibody (1:5000) for 1 hour at RT. The ECL Prime Western Blotting System was used to visualize protein bands (#RPN2232; GE Healthcare). Protein levels from test samples were compared to the loading controls (actin, GAPDH, or vinculin). To do this, densities were calculated by multiplying the average intensity by the surface of each band, and the percentage of control was calculated using the following formula: marker of interest total density x 100 / loading control total density. For each experimental sample, values were then normalized to a control which was given the value of 1.00. Statistical Analysis Paired t-test was used to compare the protein levels of SFRP2 between pancreatic tumor samples and SFRP2 protein levels in matched, normal adjacent tissue. Calculation of Spearman correlation coefficient was conducted by using the Spearman correlation coefficient equation ρ = 1- (6Σdi2) / (n(n2-1)) after ranking the level of SFRP2 mRNA expression and the ESTIMATE stromal expression, and after ranking the level of SFRP2 immunohistochemical staining and fibrosis level by Masson trichome and picrosirius red staining. Statistical analyses were performed using Stata (version v16.1, College Station, TX, USA). P-values of <0.05 were considered statistically significant. The results of the experiments are now described. SFRP2 RNA levels are the highest in pancreatic cancer and are associated with poor survival SFRP2 protein is present in multiple cancers including angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, lung, ovarian, and pancreatic cancers (A. Courtwright et al., Cancer Res (2009) 69(11):4621-8). Therefore, experiments first assessed which cancer had the highest SFRP2 expression levels. To evaluate SFRP2 mRNA levels, the RNAseq data from the TCGA was used. RNAseq data was collected for SFRP2 expression from all 32 cancer types in the database (Figure 1A). The median number of samples for each cancer type was 294 (range 36-1,082). Pancreatic cancer was found to have the highest levels of SFRP2 mRNA compared to all other tumor types, with a median expression of 13,155 RNAseq by expectation maximization (RSEM) (5.11-120,416 RSEM). In the vast majority of tumor samples among the 32 types of cancer, the SFRP2 gene was not mutated. Next, the mRNA expression levels were compared between normal pancreas and pancreatic adenocarcinoma using the GEPIA online tool. Pancreatic adenocarcinoma mRNA expression data were obtained from the TCGA RNAseq database (n=179), and normal pancreas mRNA expression data were from the GTex RNAseq database (n=177). SFRP2 mRNA levels in pancreatic adenocarcinoma were significantly higher than in normal pancreas (p<0.01; Figure 1B). The GEPIA online tool was used to evaluate the association between SFRP2 mRNA expression and disease-free survival for pancreatic cancer patients. HighSFRP2 mRNA levels were defined as SFRP2 mRNA expression in the 50thpercentile orhigher, and low SFRP2 mRNA levels were defined as SFRP2 mRNA expression in the 20thpercentile or lower. Disease-free survival was compared between high SFRP2 mRNA levels (n=89) and low SFRP2 mRNA levels (n=36) using the Kaplan-Meier method. High SFRP2 mRNA levels were associated with significantly decreased disease-free survival (hazard ratio = 2.6; p=0.0097; Figure 1C). SFRP2 protein and its receptor, FZD5, are expressed in pancreatic cancer cell lines in vitro This study previously showed that frizzled-5 (FZD5) is the receptor for SFRP2 in the non-canonical WNT- calcineurin pathway in endothelial, angiosarcoma, and breast cancer cells (Y.K. Peterson et al., Angiogenesis (2017), 615-628). Therefore, SFRP2 and FZD5 protein levels were measured in pancreatic cell lines. Both KRAS and p53 mutation-bearing cell lines were selected, since they are the most common mutations in pancreatic cancer, with a rate of 90% and 75%, respectively for each marker (S.A. Sastra and K.P. Olive, Methods Mol Biol 980 (2013), 249-66). SFRP2 and FZD5 protein levels were assessed by western blot in two human pancreatic cancer cell lines, AsPC-1 and MIA-PaCa2, and one murine cell line, Panc02-luc. SFRP2 and FZD5 protein levels were further compared to the levels in SVR angiosarcoma, used as a positive control (Y.K. Peterson et al., Angiogenesis (2017), 615-628). PBS and media were used as negative controls. All three pancreatic cell lines showed high SFRP2 and FZD5 protein levels compared to the positive control, with no protein in the negative controls (Figure 1D). KRAS regulates SFRP2 protein in PDAC cells To determine whether mutant KRAS influences SRFP2 expression, the recently described R15 monobody was utilized to directly inhibit oncogenic RAS activity in PDAC cells (Figure 2A) (I. Khan et al., Cell Reports (2022) 38(6):110322). DOX-induced expression of R15 in either PANC-1R15or PSN-1R15led to a reduction in SRFP2protein levels. In addition, PANC-1R15xenograft tumors treated with the monobody contained lower SFRP2 levels than untreated tumors (Figure 2A), further supporting regulation of SFRP2 expression by mutant KRAS signaling in PDAC. To confirm this result with a different KRAS inhibitor, PANC-1 cells were treated with MRTX1133, a non-covalent and selective inhibitor of KRASG12D, for periods of time ranging from 0 to 48 hours. As shown in Figure 2B, MRTX1133 reversibly inhibited the activity of ERK, a known target of KRASG12D, and reduced the expression SFRP2, with a maximum effect at 4 hours. To further evaluate downstream mediators of the KRAS pathway, MIA PaCa-2 cells were treated with dabrafenib (B-Raf inhibitor) and trametinib (MEK inhibitor), which reduced phospho-ERK and SFRP2 protein levels (Figure 2C). Likewise, the inhibition of PI3Kinase by buparlisib, another downstream target of KRAS, reduced phospho-AKT and SFRP2 protein levels (Figure 2D). This demonstrates that in pancreatic cancer, SFRP2 is regulated by both KRAS / RAF / MEK / ERK and KRAS / PI3Kinase pathways. SFRP2 protein expression is increased in human pancreatic cancer compared to adjacent normal pancreatic tissue To compare SFRP2 protein expression levels in human pancreatic cancer to matched normal adjacent pancreatic tissue, the levels of SFRP2 protein were measured by western blot in 23 pairs of samples. Table 5 shows the clinical characteristics of these patients. Forty-two percent were male, and the median age was 67.5 (range 47-87). Seventy five percent of the patients were Caucasian while the remaining 25% were non- Hispanic Blacks. Seventy-five percent of patients had Stage IIB disease (ranged from IA to IIB). The densitometry of SFRP2 protein bands was measured in tumor and normal tissues and normalized to the loading control, GAPDH, for each tumor and matched normal tissue assessed. Results showed significantly higher expression of SFRP2 in tumor tissues with an average percent GAPDH of 57.0 ± 5.69 % compared to 27.8 ± 7.86 % in the normal adjacent tissue (p=0.0003; n=23; one patient sample was excluded from the analysis due to poor quality of the sample; Figure 3A-Figure 3B and Figure 7).

[0002] Table 5. Clinical Characteristics of Patients Analyzed SFRP2 expression is associated with fibrosis in pancreatic cancer Pancreatic cancer has the highest stroma content of any solid organ tumor, which is a major barrier to chemotherapy tumor biodistribution (D. Thomas and P. Radhakrishnan, Mol Cancer (2019), 14 ). Since SFRP2 is associated with fibrosis in other pathologies (M. Mastri et al., Am J Physiol Cell Physiol 306 (2014), C531-9), including cancers (K.M. Vincent and L.M. Postovit, Sci Rep 7 (2017), 42719), it was examined whether SFRP2 expression levels would be associated with the degree of fibrosis in pancreatic cancer. SFRP2 mRNA expression from pancreatic cancer patients in the TCGA (n=176, consisting of 95 men, 80 women, and 1 unknown) was correlated with the ESTIMATE stromal score (ESTIMATE: Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data), and the Spearman correlation coefficient between SFRP2 mRNA expression levels and stromal score was 0.81 (Figure 4). Next, experiments were used to test the correlation between fibrosis in pancreatic tumors and SFRP2 protein expression in tumors in vivo. KPC mice (n=8) developed PDAC about 4-5 months after Cre-recombinase induction with tamoxifen. After autopsy (average 153 days after induction with tamoxifen, range 116-203 days), pancreatic tumors were resected and paraffin-embedded for staining. Masson trichome staining and picrosirius red were used to determine the degree of fibrosis in the tumors. SFRP2 staining was also performed in consecutive sections. Tumors were ranked by their degree of fibrosis, and SFRP2 staining was ranked by intensity level. Fibrosis was associated with SFRP2 staining with a Spearman correlation coefficient of 0.75 (Figure 5). Taken together, analysis of human pancreatic cancer datasets and tumors from genetically engineered mouse models demonstrate a strong correlation between SFRP2 expression and the degree of stromal expansion in pancreatic tumors. SFRP2 promotes the mesenchymal transformation of fibroblasts Because a positive correlation between SFRP2 levels and fibrosis was consistently observed, and since SFRP2 is connected to epithelial-mesenchymal transition (EMT) in network analysis (M. Mastri et al., Am J Physiol Cell Physiol (2014), C531-9), it was examined whether SFRP2 induces a mesenchymal transformation in fibroblasts. To test this, two cell types were used: normal human skin fibroblasts and normal mouse pancreatic fibroblasts. Cells were treated for 48 hours either with TFGβ (5 nM; positive control), or with SFRP2 (30 nM), or were not treated (negative control). Whole cell lysates were screened for N-cadherin and fibronectin protein expression by western blot. The protein levels of the first mesenchymal marker tested, N-cadherin, were approximately 2-fold higher in TGFβ- and SFRP2-treated skin fibroblasts compared to untreated control. A similar result was obtained for mouse pancreatic fibroblasts with a 2- fold increase in N-cadherin protein levels with TFGβ treatment, and a 3-fold increase with SFRP2 treatment (Figure 6A). The protein levels of the second mesenchymal marker tested, fibronectin, were increased by 2-fold and 5-fold in TGFβ- and SFRP2- treated human fibroblasts, respectively (Figure 6B). Although not as robust, an increase in fibronectin protein levels with both TGFβ (80%) and SFRP2 (50%) in mouse pancreatic fibroblasts was observed. These results demonstrate that like TGFβ, a well- known EMT inducer, SFRP2 plays a role in the EMT process, at least by inducing the upregulation of mesenchymal markers. SFRP2 is a biomarker for pancreatic cancer The challenges surrounding pancreatic cancer treatment lie in its tremendous resistance to chemotherapeutics. The dense stroma of pancreatic cancer is a key contributor to this resistance, establishing an environment with low vascularity that impedes drug delivery and immune cell infiltration (D. Thomas and P. Radhakrishnan, Adv Exp Med Biol 1234 (2020), 57-70). In this study, results showed SFRP2 to be highly expressed in pancreatic cancer compared to normal adjacent pancreatic tissue, and high SFRP2 expression was predictive of worse survival using a TCGA data set. Based on these findings, a future prospective clinical study to confirm the high and low cutoffs will need to be obtained in future prospective clinical trials. SFRP2 as a reliable biomarker is warranted. SFRP2 also correlated with pancreatic cancer fibrosis, and fibroblasts treated with SFRP2 protein expressed higher levels of mesenchymal markers involved in EMT, a phenotype that correlates with cancer invasion and metastasis. Previous analysis of the TCGA RNAseq data showed SFRP2 levels to be inversely correlated with survival in 14 cancer types with the highest hazard ratio being pancreatic cancer (D. Garcia et al., Ann Surg Oncol 26 (2019), 4782-4790). With the TCGA RNAseq data, results showed that SFRP2 expression levels are the highest in pancreatic cancer. Conversely, both SFRP2 mRNA and protein levels appeared to be significantly lower in normal pancreatic tissue, compared to adjacent tumor tissue. This suggests that the neoplastic transformation of the pancreatic tissue correlates with an upregulation of SFRP2. KRAS mutation is the most frequent mutation in PDAC, occurring in more than 90% of tumors (B. Giri, et al., Curr Opin Gastroenterol 33 (2017), 404-410), and data show that SFRP2 protein levels in PDAC are regulated by KRAS activity. SFRP2 has the potential to serve as a prognostic biomarker and is a potential therapeutic target, which both warrant further investigation. This study showed that fibroblasts treated with SFRP2 had increase protein levels of N-cadherin and fibronectin, similar to TGFβ. Both N-cadherin and fibronectin are well-known mesenchymal markers involved in migration and invasion during tumor progression (D. Thomas and P. Radhakrishnan, Mol Cancer 18 (2019), 14). TGFβ is one of the strongest promoters of EMT, and it upregulates N-cadherin, leading to E-cadherin / N-cadherin ratio switching from E-cadherin being the dominant cadherin expressed in epithelial cells to N-cadherin being mainly expressed in mesenchymal cells (Y. Ma et al., Cancer Lett (2018), 201-214). Upregulation of N-cadherin plays a larger role in cancer metastasis compared to loss of E-cadherin (S. Islam et al., J Cell Biol 135 (1996), 1643-54; S. Nakajima et al., Clin Cancer Res (2004), 4125-33). The observation that SFRP2 and TGFβ have similar effects on fibroblasts suggests that SFRP2 affects the mesenchymal status of the cells. A previous study on wound healing demonstrated that fibroblasts are predominant in the wound during the proliferation stage (F.Z. Gharbia et al., Sci Rep 13 (2023), 886). Importantly, this study showed that fibroblasts have the highest gene expression of EMT markers while concomitantly, SFRP2 is one of the most upregulated plasma membrane proteins. In the setting of cancer, Guo and colleagues (M. Guo et al., Oncogene 40 (2021), 5066-5080) demonstrated that SFRP2 promotes a mesenchymal phenotype in glioblastoma characterized by increased expression of mesenchymal genes in SFRP2-overexpressing cells, as well as increased SFRP2 in the mesenchymal-glioblastoma subtype. These results suggest a general function of SFRP2 as an EMT promoter during tumor progression in multiple cancers, a hypothesis that aligns with the previous observation that the inhibition of SFRP2 limits metastatic spread (P. Nasarre et al., Cancers (Basel) 13 (2021), 13(11), 2696). SFRP2 has been highly associated with fibrosis and EMT in other tumor Types (K.M. Vincent and L.M. Postovit, Sci Rep 7 (2017), 42719). Sun and colleagues’ investigation into cancer resistance after chemotherapy showed that SFRP2 was upregulated in CAFs subjected to cytotoxic therapy (Y. Sun et al., Oncogene 35 (2016), 4321-34). They also showed that WNT16B signaling is also enhanced, which further contributes to drug resistance. Inhibition of SFRP2 may dually affect chemoresistance by decreasing the tumor stroma, and decreasing the signaling that confers therapeutic resistance. There has been recent interest in targeting the stromal tissue for pancreatic cancer treatment to dismantle the barricade to chemotherapy and immune response. The results of therapeutics used for these effects have been contradictory thus far. A small molecule inhibitor of the sonic hedgehog pathway showed efficacy in preclinical studies (K.P. Olive ET AL., Science 324 (2009), 1457-61) but failed to demonstrate improved survival in clinical trials (A. De Jesus-Acosta et al., Br J Cancer 122 (2020), 498-505; A.H. Ko et al., Pancreas 45 (2016), 370-5). Meanwhile, some improvements have been observed with other stromal inhibitors in phase I / II trials targeting TGFβ (D. Melisi et al., Br J Cancer 119 (2018), 1208-1214) and the angiotensin II receptor (J.E. Murphy et al., JAMA Oncol 5 (2019), 1020-1027). Conversely, Ozdemir and collaborators found that depleting myofibroblasts in a pancreatic cancer GEMM resulted in increased infiltration of regulatory T-cells and worse survival (B.C. Ozdemir, Cancer Cell 25 (2014), 719-34). These results suggest that complete disruption of the tumor microenvironment may not bear the desired results of enhancing therapeutic efficacy. Investigation of pancreatic CAFs has shown that this is a heterogeneous population of cells with different functions, which likely contributes to these different findings. Although Ozdemir and colleagues found that myofibroblast depletion led to more aggressive tumors and immune dysregulation, they also discovered that treating these myofibroblast-depleted mice with CTLA-4 checkpoint inhibitors led to less undifferentiated cancer cells, normalized parenchyma, and improved survival compared to non- myofibroblast depleted mice treated with anti-CTLA-4 antibody (B.C. Ozdemir, Cancer Cell 25 (2014), 719-34). Therefore, inhibiting the stroma may need to be accompanied by immunotherapy for efficacy, and further studies will identify whether targeting the stroma overcomes resistance to immunotherapy in pancreatic cancer. Previously it has been shown that SFRP2 affects immune dysregulation, specifically increasing transcription of CD38, which reduces resistance to the PD-1 inhibition (P. Nasarre et al., Cancers (Basel) 13 (2021), 13(11), 2696). Therefore, targeting SFRP2 may have the added benefit of providing immunotherapy, in conjunction with stromal regulation, inducing tumor apoptosis and inhibiting angiogenesis. Since SFRP2 is highly expressed in pancreatic cancer; its expression is significantly associated with worse survival, and it is regulated by KRAS; SFRP2 may serve as a novel therapeutic target for pancreatic cancer. This study demonstrated that SFRP2 is highly expressed in pancreatic cancer and its expression is significantly associated with worse disease-free survival and is regulated by KRAS. Experiments confirmed that, like other cancer types, SFRP2 is associated with fibrosis in pancreatic cancer. Investigation of SFRP2’s impact on fibroblasts showed that SFRP2 stimulates EMT, which identifies an additional role for SFRP2 as a regulator for cancer invasion, angiogenesis, metastasis, and ECM construction. Targeting the stroma is a promising avenue for pancreatic cancer treatment, but the current literature demonstrates that further research on the communication of all heterogeneous cell populations, cytokines, and proteins in the tumor microenvironment is needed to understand how best to manipulate it to improve survival. SFRP2 is one such protein that plays a part in this crosstalk and merits additional study to determine its potential as a regulator for both stroma production and immune dysregulation. Example 2: Secreted frizzled related-protein 2 is regulated by KRAS in lung cancer cells. KRAS, a pivotal protein in cellular signaling pathways, plays a crucial role in cell growth and differentiation. Among patients with non-small cell lung cancer (NSCLC), approximately 23% exhibit KRAS mutations, with the G12C mutation being the prevailing variant. Notably, the G12C-mutant KRAS (KRASG12C) remains persistently activated, a state closely linked to cancer development (Lee et al., 2022, Targeted oncology, 17(6), 727–733). To evaluate whether KRAS regulates SFRP2 protein, the NCI-H358 KRASG12CLung Cancer Cell line was used. Cells were treated with either control (PBS) or the KRAS inhibitor ARS16201 µM for 6 hours. At the end of the experiment, cells were lysed and subjected to Western blot probing with an antibody to SFRP2, phosphor-ERK, and vinculin (loading control). The phosphor-ERK is a positive control, as there should be a decrease in phospho-ERK when KRAS is inhibited. The results of the Western blot show that there is a decrease in both phospho- Erk and SFRP2 at 6 hours (Figure 8). This shows that KRASG12Cis a regulator of SFRP2 in lung cancer cells. The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

CLAIMS What is claimed is:

1. A method of treating or preventing a disease or disorder in a subject, the method comprising: a) detecting the level of Kirsten rat sarcoma viral oncogene homologue (KRAS) signaling in a sample; b) comparing the level of KRAS signaling to the level in a comparator control; c) diagnosing the subject as having or at risk of developing a disease or disorder when the level of KRAS signaling is increased as compared to the comparator control; and d) administering to the subject an inhibitor of SFRP2 for the treatment or prevention of the diagnosed disease or disorder.

2. The method of claim 1, wherein the inhibitor of SFRP2 comprises an anti- SFRP2 antibody comprising a complementary determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:19, a CDR H2 comprising the amino acid sequence of SEQ ID NO:20, a CDR H3 comprising the amino acid sequence of SEQ ID NO:21, a CDR LI comprising the amino acid sequence of SEQ ID NO:22, a CDR L2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:

24.

3. The method of claim 1, wherein the comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level of KRAS signaling in a control population.

4. The method of claim 1, wherein the disease or disorder is pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer.

5. The method of claim 4, wherein the disease or disorder is pancreatic adenocarcinoma.

6. The method of claim 4, wherein the disease or disorder is lung cancer.

7. The method of any one of claims 1-6, wherein the subject is human.

8. A method of diagnosing a subject with a disease or disorder, the method comprising: a) detecting the level or activity of secreted frizzled-related protein 2 (SFRP2) in a sample, comparing the level or activity of SFRP2 to the level in a first comparator control, b) detecting the level of Kirsten rat sarcoma viral oncogene homologue (KRAS) or KRAS signaling in a sample, comparing the level of KRAS or KRAS signaling to the level in a second comparator control, and c) diagnosing the subject as having or at risk of developing a disease or disorder when the level or activity of the combination of SFRP2 and KRAS or KRAS signaling is increased as compared to the comparator control.

9. The method of claim 8, wherein the first comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level or activity of SFRP2 in a control population, and the second comparator control is at least one selected from the group consisting of: a positive control, a negative control, a reference standard, a historical control, a historical norm, or the level of KRAS or KRAS signaling in a control population.

10. The method of claim 8, wherein the disease or disorder is pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer.

11. The method of claim 8, wherein the disease or disorder is pancreatic adenocarcinoma.

12. The method of claim 8, wherein the disease or disorder is lung cancer.

13. A method of treating or preventing a disease or disorder in a subject, the method comprising the method of any one of claims 8-12, further comprising administering to the subject a composition for the treatment or prevention of the diagnosed disease or disorder.

14. The method of claim 13, wherein the composition comprises an inhibitor of SFRP2, an inhibitor of KRAS signaling or a combination thereof.

15. The method of claim 14, wherein the inhibitor comprises a chemical compound, a protein, a peptide, a peptidomimetic, an antibody, an antibody fragment, an antibody mimetic, a chimeric antibody, a bispecific antibody, a ribozyme, a small molecule chemical compound, a short hairpin RNA, RNAi, siRNA, miRNA, or a nucleic acid encoding an antisense nucleic acid molecule.

16. The method of claim 14, wherein the method further comprises administering a combination of a) Sotorasib, adagrasib or MRTX1133 and b) an anti- SFRP2 antibody.

17. The method of claim 14, wherein the inhibitor of SFRP2 comprises an anti-SFRP2 antibody comprising a complementary determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:19, a CDR H2 comprising the amino acid sequence of SEQ ID NO:20, a CDR H3 comprising the amino acid sequence of SEQ ID NO:21, a CDR LI comprising the amino acid sequence of SEQ ID NO:22, a CDR L2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR L3 comprising the amino acid sequence of SEQ ID NO:24.

18. The method of claim 13, further comprising the step of administering to the subject at least one additional therapeutic or prophylactic agent.

19. The method of claim 13, wherein the disease or disorder is at least one selected from the group consisting of pancreatic, lung, breast, osteosarcoma, angiosarcoma, hepatocellular carcinoma, prostate, colon, renal, ovarian or urogenital cancer.

20. The method of claim 19, wherein the disease or disorder is pancreatic adenocarcinoma.

21. The method of claim 19, wherein the disease or disorder is lung cancer.

22. The method of claim 13, wherein the subject is human.

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