93 results about "Resistant cancer" patented technology

The present disclosure provides methods to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds can be used to sensitize resistant cancer cells or decrease the proliferation of cells. The compounds can target proteins in the DNA damage repair pathway leading to a decrease in DNA damage repair in target cells.

The present disclosure provides methods to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds can be used to sensitize resistant cancer cells or decrease the proliferation of cells. The compounds can target proteins in the DNA damage repair pathway leading to a decrease in DNA damage repair in target cells.

This invention discloses a butyrolactone compound with multidrug resistance reverse transcription activity, its preparation method, and its uses. The compound's structural formula is shown in Figure I. The preparation method includes the following steps: fermenting *Aspergillus pyrolyticus* (accession number CCTCC NO: M2014086) to obtain a butyrolactone fermentation product; extracting the fermentation product with ethyl acetate to obtain a crude extract; degreasing the crude extract with hexane and dichloromethane to obtain a final extract; and purifying the final extract using normal-phase silica gel column chromatography, reversed-phase medium-pressure column chromatography, and reversed-phase semi-preparative high-performance liquid chromatography. The advantage of this butyrolactone compound is that it possesses multidrug resistance reverse transcription activity and the ability to regulate P-gp-mediated drug efflux in multidrug-resistant cell lines, making it a potential drug for treating multidrug-resistant cancers.

Provided are anti-ABCB 1 antibodies that may be used as multi-specific, including bispecific, antibodies targeting both ABCB 1 and a tumor-associated antigen (TAA), as well as pharmaceutical compositions, nucleic acids, recombinant expression vectors, cells, and kits that include or encode such antibodies and multi-specific antibodies. Further included are uses and methods of treating conditions where inhibition of ABCB 1-mediated efflux transport is desirable, such as, cancer or multi-drug resistance mediated by the ABCB1 transporter, e.g., multi-drug resistant cancer. In particular, the disclosure provides humanized multi-specific, e.g. bispecific, IgG (IgG1) antibodies that bind ABCB1 and a TAA. Multi-specific IgG1 antibody molecules are provided with Fc substitutions in at least one of a first and a second heavy chain constant region.

Embodiments of the instant disclosure relate to novel methods and compositions for treating tumors resistant to immune checkpoint inhibitors. In certain embodiments, compositions herein can have at least one nanoparticle formed of Prussian blue materials and, optionally, one or more CD137 agonists. In other embodiments, methods of treating tumors herein can include administering an effective amount of at least photothermal therapy agent in combination with at least one CD137 agonist separately or in a combination therapy / combination composition.

The present invention relates to a method for treating gefitinib and / or erlotinib resistant cancer. Cancer patients are monitored for cancer development after treatment with gefitinib and / or erlotinib. The development of cancer indicates that the cancer is resistant to gefitinib and / or erlotinib. Once it is shown that the cancer is developing, a pharmaceutical composition containing an irreversible epidermal growth factor receptor (EGFR) inhibitor is administered to the patient. In a preferred embodiment, the irreversible EGFR inhibitor is EKB-569, HKI-272 and HKI-357.

The present invention is directed to methods of sensitizing tyrosine kinase inhibitor (TKI)-resistant cancer cells in a subject using a SWI / SNF complex modulator.

Provided are methods for treating treatment-resistant non-small-cell lung cancer (NSCLC) in a patient in need thereof comprising administering a chimeric antigen receptor (CAR) cell therapy, antibody drug conjugate (ADC), or bispecific T cell engager (BiTE) targeting ALPP and / or ALPPL2 in the NSCLC cell, and / or a therapy targeting a genetic mutation selected from an EGFR mutation, a KRAS mutation, a RET mutation, an ALK mutation, a HER2 mutation, a MET mutation, a MEK mutation, an AKT mutation, an ERK mutation, a CDK4 / 6 mutation, a BRAF mutation, and an FGFR mutation.

Substituted pyrrolo[2,3-d]pyrimidines as inhibitors for multi-resistant cancers are described herein. Also provided herein are methods of forming the compounds, methods for inhibiting aurora kinase A and / or aurora kinase B activity and epidermal growth factor activity, methods of treating, ameliorating, or preventing cancer, and uses of the compounds for inhibiting aurora kinase A and / or aurora kinase B activity and epidermal growth factor receptor kinase activity. The compounds are generally of the formulas as illustrated herein, including those of Formula (I-2) or a pharmaceutically acceptable salt thereof:wherein: X1 is N; X2 is N; X3 is —NH—; X4 is N or CR2; X5 is CH, CCH3, or CCOOH; L1 is —NR4—R1; L2 is NH2 or H; R1 is:R2 is H, COOH, a 5-membered heteroaryl, or X6R3; X6R3 is as described herein; R4 is H; R5 is as described herein; and m is 1, 2, 3, 4, or 5.

The present invention represents a novel hybrid of the two natural products sclareol and doxorubicin, in the form of their conjugates. These compounds are in the form of conjugates wherein doxorubicin and sclareol are covalently linked by a linker in a molar ratio of 1: 1. The hybrid has been shown to have anti-cancer properties and is effective in the treatment of cancer cells resistant to a P-glycoprotein membrane transporter responsible for resistance to doxorubicin. Hybrid have been tested on different types of cell lines, including human glioblastoma, non-small cell lung cancer, and colorectal cancer. The invention further relates to a method for the production thereof and to the use thereof in pharmaceutical products or pharmaceutical preparations. The research results include the cytotoxic activity of single compounds, combined compounds, and conjugated compounds in sensitive and resistant cancer cell pairs with and without P-glycoprotein expression. The selectivity to cancer cells is determined by comparison with commercially available normal human lung fibroblasts. The study also studies the nanoparticle properties of the hybrids, their intracellular localization and in vivo toxicity.

The present invention relates to a composition for inhibiting multidrug resistance, the composition containing an autocrine motility factor (AMF) as an active ingredient. Specifically, treating cancer cells with an AMF protein or an AMF peptide inhibits the mRNA and protein expression of P-glycoprotein or multidrug resistance related protein-1 (MRP-1), which are major causes of multidrug resistance, and administering the AMF protein or AMF peptide in combination with an anticancer agent inhibits the release of the anticancer agent from cells, thus having the effect of increasing the accumulation of the anticancer agent inside cancer cells. Therefore, the composition can be effectively used as a pharmaceutical composition for inhibiting multidrug resistance to an anticancer agent or as an anticancer adjuvant for multidrug-resistant cancer.

To provide a therapeutic agent for PARP inhibitor-resistant cancer.SOLUTION: The present invention relates to a pharmaceutical composition for treating or preventing a solid cancer patient having resistance to a PARP inhibitor, and the pharmaceutical composition according to the present invention can effectively reduce the size of a tumor in a patient having resistance to a PARP inhibitor.SELECTED DRAWING: Figure 4

Embodiments disclosed herein use forward genetics tools (e.g., ORF libraries, perturbation libraries) to study fitness advantages under immune pressure, including resistance mechanisms. Once the resistance mechanisms are identified, vulnerabilities (i.e., dependencies) in resistant cells can be identified (e.g., synthetic lethality screens in resistant cancer cells). For example, drug or CRISPR screening can be performed in cells with an identified resistant state. Embodiments disclosed herein also provide targets for resistance to IFN-y treatment.

The present invention relates to combination therapies for treating cancer, optionally chemotherapy-resistant cancer, in a subject. The combination therapy comprises (a) an antibody or antigen-binding portion thereof that specifically binds to CD40, and (b) a chemotherapy. The invention also relates to pharmaceutical compositions, kits and methods of using such therapies.

The present invention relates to combination therapies for treating cancer, optionally chemotherapy-resistant cancers, in a subject. The combination therapies comprise (a) an antibody or antigen-binding portion thereof that specifically binds to CD40, and (b) chemotherapy. The invention also relates to pharmaceutical compositions, kits and methods of using such therapies.

The present invention relates to a pharmaceutical composition for preventing or treating anticancer drug-resistant cancer, containing rucaparib camsylate as an active ingredient. Rucaparib camsylate can function as an immune checkpoint inhibitor by blocking the binding of PD-1 and PD-L1, and thus can be effectively used in pharmaceuticals for the prevention or treatment of cancer. In addition, rucaparib camsylate according to the present invention has an excellent anticancer effect against uterine sarcoma cancer that exhibits resistance to doxorubicin, and thus can be very effectively used for the prevention or treatment of resistant cancer.

The present invention provides, inter alia, methods, pharmaceutical compositions and kits for treating or ameliorating the effect of cancer in a subject that is refractory or resistant to non-ERK MAPK pathway inhibitor therapy. Also provided are methods for identifying subjects with cancer that would benefit from therapy with an ERK inhibitor and for inhibiting phosphorylation of RSK in cancer cells that are refractory or resistant to a non-ERK MAPK pathway inhibitor.

To provide compositions and methods for treatment of chemoresistant cancer (breast cancer).SOLUTION: Provided are methods that include administering to a subject in need a therapeutically effective amount of a chemotherapeutic agent and a ROR-1 antagonist. Further provided are pharmaceutical compositions including a chemotherapeutic agent, a ROR-1 antagonist and a pharmaceutically acceptable excipient. In embodiments, the chemotherapeutic agent is paclitaxel and the ROR-1 antagonist is cirmtuzumab.SELECTED DRAWING: Figure 5A

The present invention is directed to methods of sensitizing tyrosine kinase inhibitor (TKI)-resistant cancer cells in a subject using a SWI / SNF complex modulator.

The present invention relates to a composition for the prevention or treatment of cisplatin-resistant cancer comprising an inhibitor of DUSP23 expression or activity as an active ingredient. It was found that DUSP23 expression is upregulated in cell clusters exhibiting characteristics of cancer stem cells, and that knocking down DUSP23 significantly reduces cell cluster formation as well as decreases the expression of SOX2, a major stem cell marker. Furthermore, DUSP23 expression was increased in lung cancer cells that had developed cisplatin resistance, and it was confirmed that the downregulation of DUSP23 inhibits self-renewal and invasive capabilities during the induction of cancer cell death. In addition, it was confirmed that DUSP23 plays an important role in promoting cancer stem cell characteristics through SOX2 expression. In conclusion, it has been shown that targeting DUSP23 can be a promising therapeutic strategy to overcome anticancer drug resistance in lung cancer, and the composition of the present invention is expected to be usefully utilized as a treatment for lung cancer cells with cisplatin resistance.

Most of therapeutic failures in chemotherapy during cancer invasion and metastasis are attributed to drug resistance. The inventors aimed to investigate the potential of targeting the secreted protein, eAGR2 as a novel adjuvant strategy to enhance the effectiveness of chemotherapy and overcoming chemoresistance in cancer therapy. Remarkably, extracellular AGR2 (eAGR2) demonstrated the ability to enhance resistance to both (doxorubicin and tamoxifen) treatments. Furthermore, even in the case of drug-resistant cancer cells that exhibited inherent resistance to chemotherapy, supplementation with an AGR2-blocking antibody restored sensitivity to tamoxifen in vitro. Thus, the inventor shed light on previously unknown chemotherapy resistance in resistant breast cancer cells, which can be effectively overcome by blocking eAGR2. Consequently, the inhibition of eAGR2 emerges as a promising adjunctive approach for concurrent administration alongside existing first- and second-line cancer therapies. This not only has the potential to bolster the efficacy of chemotherapy but also to prevent tumour chemoresistance.

Small molecule ERα biomodulators that kill therapy-resistant ERα positive breast, ovarian, and endometrial cancer cells are disclosed. In one embodiment, the small molecule biomodulator has increased therapeutic utility because of an increased ability to kill therapy-resistant cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen, and fulvestrant / ICI). The small molecule biomodulators not only inhibit proliferation of the cancer cells but kills them, which prevents reactivation of tumors years later. Compounds of the invention, such as ErSO-TFPy, are effective for treating ERα positive cancers such as breast cancer, ovarian cancer, uterine cancer, cervical carcinoma, endometrial cancer, and the like.

The invention discloses a formamide pyrazole compound as well as a pharmaceutical composition and application thereof. The compound has a structure as shown in a formula (I), has relatively strong anti-proliferative activity on a TRK xDFG mutation drug-resistant cell strain Ba / F3-LMNA-NTRK1-G667C, can effectively down-regulate the TRKAG667C protein level in a Ba / F3-LMNA-NTRK1-G667C cell, has an application value as a TRK degradation agent, is used for preparing an anti-tumor drug, and particularly provides a new drug molecule for treating mutation drug-resistant cancers.

The invention provides compositions and methods for treating a refractory, relapsed or resistant cancer or a chronic infectious disease. In particular the present invention relates to a modified immune cell with reduced SUV39H1 activity, for use in the treatment of a patient suffering from a refractory, relapsed or resistant cancer or suffering from a chronic infectious disease, wherein the cell expresses one or more engineered antigen-specific receptors that bind an antigen associated with the cancer or the chronic infectious disease

The present invention features methods for increasing sensitivity and / or reversing resistance to chemotherapy, methods for treating or preventing a cancer in a subject, methods for treating clonal hematopoiesis of indeterminate potential in a subject, and methods of identifying resistance or sensitivity to chemotherapy in a subject. In some embodiments, the methods contain the step of administering an agent that inhibits the expression or activity of a Protein phosphatase 1D (PPM1D) polypeptide or polynucleotide. The present invention also features compositions for increasing sensitivity and / or reversing resistance to chemotherapy.

The present invention discloses a method of treating a CDK4 / 6 inhibitor resistant estrogen receptor alpha positive cancer in a subject having a wild-type estrogen receptor alpha and / or a mutant estrogen receptor alpha, the method comprising administering to the subject a therapeutically effective amount of elastrant, or a pharmaceutically acceptable salt or solvate thereof, wherein the mutated estrogen receptor alpha comprises one or more mutations selected from the group consisting of D538G, Y537X1, L536X2, P535H, V534E, S463P, V392I, E380Q, and combinations thereof, wherein: X1 is S, N, or C; and X2 is R or Q. In some embodiments, the CDK4 / 6 inhibitor resistant estrogen receptor alpha positive cancer is selected from the group consisting of breast cancer, uterine cancer, ovarian cancer, and pituitary cancer.

The invention represents new hybrid compounds of two natural products sclareol and doxorubicin in the form of their conjugates. These compounds are in the form of conjugates, where doxorubicin and sclareol are covalently linked by a linker in a 1:1 molar ratio. The hybrids have shown to possess anticancer properties and are effective in treating resistant cancer cells that have P-glycoprotein membrane transporter, responsible for resistance to doxorubicin. The hybrids have been tested on different types of cell lines, including human glioblastoma, non-small cell lung carcinoma, and colorectal carcinoma. Also, a method for their preparation and their use in medical products or pharmaceutical preparations has been determined. The results of the study include the cytotoxic activity of single, combined, and conjugated compounds in pairs of sensitive and resistant cancer cells, with and without P-glycoprotein expression. The selectivity towards cancer cells was determined by comparing with commercially available normal human lung fibroblast cells. The study also investigated the nanoparticle nature of hybrid compounds, their intracellular localization and toxicity in vivo.

The present invention relates to a pharmaceutical composition for the prevention or treatment of anticancer-agent-resistant cancer, containing trovafloxacin as an active ingredient. The trovafloxacin can function as an immune checkpoint inhibitor by blocking the binding between PD-1 and PD-L1, and thus can be effectively used in medicines for the prevention or treatment of cancer. In addition, the trovafloxacin according to the present invention has an excellent anticancer effect against uterine sarcoma showing resistance to doxorubicin, and thus can be very effectively used for the prevention or treatment of resistant cancer.

The invention provides an mRNA (messenger Ribonucleic Acid) medicine for inhibiting tumor stem cells and reducing the dryness of the tumor cells and a preparation method of the mRNA medicine. The mRNA medicine comprises any one or a combination of at least two of linear PTEN mRNA, self-replicating PTEN mRNA and annular PTEN mRNA; the linear PTEN mRNA comprises a 5 'UTR (Untranslated Region) sequence, a PTEN protein coding sequence and a 3' UTR sequence; the nucleotide sequence of the PTEN protein coding sequence comprises a sequence as shown in SEQ ID NO. 1. The mRNA nano-drug prepared by the invention not only has high transfection efficiency in tumor stem cells, but also can induce differentiation of the tumor stem cells and remarkably inhibit growth of the tumor stem cells; in drug-resistant tumor cells, the stemness of the drug-resistant tumor cells is inhibited, so that the sensitivity to chemotherapy, targeted antibodies, immunotherapy and the like is improved, and the killing effect of the drug is improved. The invention also shows an excellent anti-tumor effect in a human tumor cell line xenotransplantation model of the drug-resistant breast cancer in vivo, and provides a promising treatment strategy for the treatment of the drug-resistant breast cancer.

A pyridine derivative and use thereof are provided. The compound has an obvious inhibitory effect on the activity of KRAS and PI3K proteins, can be used as a KRAS and / or PI3K protein inhibitor, and can be used for preparing a drug for treatment of diseases such as KRAS or PI3K protein-mediated cancer. The compound has an extremely strong inhibitory effect on a KRAS G12C inhibitor (e.g. AMG-510) drug-resistant cancer cells, and has a wide application prospect thereof.