Method for treatment of solid tumor cancer using illudin and biomarker

Abstract

To provide a method for treating solid tumor cancer using targeted drug therapy, and a method for determining the likelihood that a subject suffering from a solid tumor cancer will benefit from treatment with an illudin.SOLUTION: There is provided a method for predicting responsiveness to treatment in a patient having a solid tumor. The method comprises: obtaining a biological sample from the patient; measuring a level of expression of PTGR1, PTPN14, ASPH, or a combination thereof in the biological sample; and comparing the level of expression in the biological sample with a level of expression in a biological sample derived from a subject not having a solid cancer, wherein an increase in the level of expression in the biological sample from the patient, relative to that from the subject not having the solid tumor, indicates a likelihood of an effective response to treatment with a compound of the following formula, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.SELECTED DRAWING: None

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 745,382, filed on October 14, 2018, which is hereby incorporated by reference in its entirety.

[0002] The present invention relates to a marker for use in determining the sensitivity of cancer patients to anti - cancer agents (e.g., illudins) administered to cancer patients, and to the application of such a marker, and the marker can determine whether the cancer patient has a therapeutic responsiveness to the anti - cancer agent.

Background Art

[0003] Illudins are chemically modified and used in the treatment of cancer. Irofulven, which is an illudin, is a chemically modified form of the mycotoxin illudin S. Irofulven is a DNA alkylating agent and has a unique mechanism. This illudin is an agent that damages DNA and proteins and targets rapidly dividing malignant tumor cells. Irofulven enters tumor cells and interferes with DNA replication and cell division by binding to DNA and protein targets. As a result, tumor cells become arrested and die (apoptosis). Studies have shown that at certain doses, tumor cells are highly sensitive to the dual damage activity of irofulven, while normal cells show only a slight response to this cell - killing agent. Not all solid cancers are sensitive to illudins, and it has been difficult to determine a method for identifying illudin - sensitive subjects.

[0004] Despite recent developments in diagnostic and treatment strategies for patients with solid tumors such as prostate cancer, ovarian cancer, liver cancer, and renal cancer, there are many significant knowledge gaps regarding screening and treatment. Knowledge about patient characteristics, including genetic profiles for optimally stratifying subjects into responsive groups at the time of diagnosis, is insufficient. Furthermore, knowledge about the risk factors for developing these cancers or dying from them is also insufficient, and there is a lack of effectively introducing real-world evidence into clinical practice. This knowledge gap means that the prediction of which subjects will have the best outcomes with a particular treatment is not optimized. In addition, current predictions about which subjects may be harmed by unnecessary or inappropriate treatment or may be managed without treatment remain poor.

[0005] Accordingly, there is a need for a method of determining a treatment method and whether a subject is responsive or potentially responsive to iridium treatment. In particular, this need is the object of the present application. Summary of the Invention

[0006] The present application relates to a method for determining the likelihood that a subject suffering from solid tumor cancer will benefit from treatment with iridium. Furthermore, it also relates to a treatment method based on such determination. In some embodiments, the markers Prostaglandin reductase 1 (PTGR1), Protein Tyrosine Phosphatase Non-Receptor Type 14 (PTPN14), Aspartate Beta-Hydroxylase (ASPH) are used in the method, either together with one or more genes or alone. In one embodiment, the protein or the gene may be expressed or methylated.

[0007] A method of treating solid tumor cancer using targeted drug therapy is

[0008] The following formula: [Chemical] identifying a patient having cancer that is sensitive to treatment with a compound of

[0009] wherein R1, R2 and R3 are independently (C1-C4) alkyl, methyl or hydroxyl.

[0010] Definitions The term "subject" refers to an animal including, but not limited to, primates (e.g., humans), cattle, pigs, sheep, goats, horses, dogs, cats, rabbits, rats or mice. The terms "subject" and "patient" are used interchangeably herein in connection with, for example, human subjects, mammalian subjects such as humans in one embodiment.

[0011] The terms "treat", "treating" and "treatment" are intended to include alleviating or eliminating one or more of the conditions or symptoms associated with the condition, or alleviating or eradicating the cause of the condition itself.

[0012] The terms "administer", "administering" and "administration" include preventing recurrence of a particular disease, disorder or condition in a patient already suffering from the disease, disorder or condition, and / or prolonging the time during which a patient suffering from the disease, disorder or condition remains in remission. The terms include modulating the threshold, development and / or duration of the disease, disorder or condition, or changing the circumstances under which a patient responds to the disease, disorder or condition.

[0013] The terms "prevent", "preventing" and "prevention" are intended to include ways of delaying and / or not causing the occurrence of an injury, disease or condition, or its attendant symptoms, ways of preventing a subject from becoming an injury, disease or condition, or ways of reducing the risk of a subject becoming an injury, disease or condition.

[0014] As used herein, and unless otherwise specified, the terms "sensitive" and "sensitive to" in relation to treatment with a compound are relative terms that refer to the degree of effectiveness of the compound in reducing or decreasing the progression of a disease, disorder or condition being treated. For example, the terms "increased sensitivity" or "sensitive to treatment" when used in relation to the treatment of a disease, injury or condition associated with a compound refer to an increase in treatment effectiveness of at least 3%, particularly at least 5% or more.

[0015] As used herein, and unless otherwise specified, the term "therapeutically effective amount" of a compound is an amount sufficient to provide a therapeutic benefit in the treatment or management of a disease, injury or condition, or an amount sufficient to delay or minimize one or more symptoms associated with the presence of a disease, disorder or condition. The therapeutically effective amount of a compound means the amount of a single therapeutic agent, or the amount of a therapeutic agent used in combination with other therapeutic agents that provide a therapeutic benefit in the treatment or management of a disease, disorder or condition. The term "therapeutically effective amount" may include an amount that improves the overall treatment, an amount that reduces or avoids the symptoms or causes of a disease, injury or condition, or an amount that enhances the therapeutic effectiveness of another therapeutic agent.

[0016] As used herein, "effective patient response" refers to any increase in the therapeutic benefit to a patient. An "effective patient response" can be, for example, a 5%, 7.5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 75%, 80%, 90% or 100% decrease in the rate of progression of a disease, disorder or condition. An "effective patient response" can be, for example, a 5%, 7.5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 75%, 80%, 90% or 100% decrease in the physical symptoms of a disease, disorder or condition. An "effective patient response" can be, for example, a 5%, 7.5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 75%, 80%, 90%, 100%, 120%, 140%, 150%, 170%, 180%, 190%, 200% or greater increase in the patient's response as measured by any suitable means such as gene expression, cell number, assay results, etc.

[0017] Improvement in a disease, disorder or condition can be characterized as complete or partial remission. "Complete remission" refers to the absence of clinically detectable disease, accompanied by normalization of any past abnormal radiological examinations, bone marrow and cerebrospinal fluid (CSF) or abnormal monoclonal protein measurements. "Partial remission" refers to at least about a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% decrease in the burden of all measurable disease, disorder or condition in the absence of new lesions (i.e., the number of malignant cells present in a subject, or the measured volume of a tumor mass, or the amount of abnormal monoclonal protein). The term "treatment" anticipates both complete and partial remission.

[0018] The term "refractory or resistant" refers to a situation where a patient does not respond to treatment, even after intensive treatment. For example, a patient may have residual cancer cells (e.g., leukemia cells or lymphoma cells) in the lymphatic, blood and / or hematopoietic tissues (e.g., bone marrow).

[0019] As used herein, the terms "determining," "measuring," "examining," "assessing," and "analyzing" generally refer to any form of measurement and include determining the presence or absence of an element. These terms include both quantitative and / or qualitative determinations. An assessment may be relative or absolute. "Assessing the presence of" may include determining any amount that is present, as well as determining whether it is present or absent.

[0020] The terms "isolated" and "purified" refer to isolating a substance (e.g., DNA / mRNA or protein) such that it makes up the majority of the sample in which the substance is present. That is, it refers to isolating a substance such that it makes up more than it typically does in its natural or unisolated state. Typically, the majority of a sample includes, for example, more than 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, or more of the sample, usually 90% to 100% or less of the sample. For example, a sample of isolated DNA / mRNA may typically contain at least about 1% of the total mRNA. Polynucleotide purification techniques are known in the art and include, for example, gel electrophoresis, ion exchange chromatography, affinity chromatography, flow sorting, and precipitation according to density.

[0021] As used herein, the term "sample" relates to a material or mixture of materials and is typically, but not necessarily, in liquid form and contains one or more components of interest.

[0022] As used herein, the term "biological sample" refers to a sample obtained from a biological subject and includes samples originating from biological tissues or fluids obtained, accessed, or collected in vivo or in situ. Biological samples also include samples derived from regions of a biological subject containing pre-cancerous or cancerous cells or tissues. Such samples can be, but are not limited to, organs, tissues, fractions, and cells isolated from mammals. Exemplary biological samples include, but are not limited to, cell lysates, cell cultures, cell lines, tissues, oral tissues, gastrointestinal tissues, organs, organelles, biological fluids, blood samples, urine samples, skin samples, etc. Biological samples include, but are not limited to, whole blood, partially purified blood, PBMC, tissue biopsies, etc.

[0023] As used herein, and unless otherwise indicated, the term "optically pure" means a composition that contains one optical isomer of a compound and substantially no other isomers of the compound. For example, an optically pure composition of a compound having one chiral center substantially contains no enantiomer of the compound on the opposite side. An optically pure composition of a compound having two chiral centers substantially contains no other diastereomers of the compound. A typical optically pure compound contains more than about 80% by weight of one enantiomer of the compound and less than about 20% by weight of the other enantiomer of the compound, or more than about 90% by weight of one enantiomer of the compound and less than about 10% by weight of the other enantiomer of the compound, or more than about 95% by weight of one enantiomer of the compound and less than about 5% of the other enantiomer of the compound, or more than about 97% by weight of one enantiomer of the compound and less than about 3% of the other enantiomer of the compound, or more than about 99% by weight of one enantiomer of the compound and less than about 1% of the other enantiomer of the compound.

[0024] As used herein, the term "irgin" refers to the following formula I:

Chemical formula

[0025] Among the members of the anti-cancer drug sensitivity determination markers, gene markers Prostaglandin reductase 1 (PTGR1), Protein Tyrosine Phosphatase Non-Receptor Type 14 (PTPN14), and Aspartate Beta-Hydroxylase (ASPH) that are used alone or in combination with one or more genes can be mentioned. In certain embodiments, the protein genes may be expressed or methylated. Prostaglandin reductase 1 (PTGR1) is a highly inducible enzyme with enone reductase activity. The PTGR1 of the marker was correlated with sensitivity to irinotecan-based treatment or with true responders to irinotecan-based treatment. By using this marker alone or in combination with others, a screening test based on predictive biomarkers that enables treatment based on personalized medicine for patients has been developed, which can reduce the gap in the treatment of cancer (e.g., prostate cancer). The inventors have found that the detection of mutant nucleic acid sequences or protein sequences related to solid tumors circulating in subjects with solid tumor cancers can accurately determine whether the subject is sensitive to treatment with irinotecan.

[0026] In certain embodiments, the DNA of the PTGR1, PTPN14, and ASPH genes is methylated. DNA methylation is a process in which a methyl group is added to a DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation often acts to suppress gene transcription.

[0027] A method of treating or managing solid tumor cancers (e.g., prostate cancer, ovarian cancer, liver cancer, kidney cancer, and thyroid cancer) is given by the following formula:

Chemical formula

[0028] A method of treating a solid tumor or managing the treatment of a solid tumor comprises the following formula:

Chemical formula

[0029] or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, and administering to the patient a therapeutically effective amount of the compound.

Chemical formula

[0030] A method for predicting responsiveness to treatment in a patient having a solid tumor, comprising obtaining a biological sample from the patient, measuring the expression level of PTGR1, PTPN14, ASPH, or a combination thereof in the biological sample, and comparing the expression level of PTGR1, PTPN14, ASPH, or a combination thereof in the biological sample with the expression level of a biological sample from a subject without a solid tumor, wherein a decrease in the expression level of PTGR1, PTPN14, ASPH, or a combination thereof in the biological sample from the patient compared to the level from a subject without a solid tumor is represented by the following formula: [Chemical Formula] A method indicating the possibility of an effective response to treatment with a compound of or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

[0031] In one embodiment herein, there is provided a method for treating or managing solid tumor cancer, comprising identifying a patient having solid tumor cancer who is sensitive to treatment with irudin, or a pharmaceutically acceptable salt thereof, and administering a therapeutically effective amount of the compound to the patient. In certain embodiments, there is provided a method further comprising administering a therapeutically effective amount of an additional active agent that is irudin herein.

[0032] In one embodiment, irudin is administered once on day 1 of a 21-day cycle or another cycle.

[0033] In another embodiment, irudin may be administered together with one or more second active ingredients. Such active ingredients may be other anti-cancer agents or agents used in the treatment of cancer patients.

[0034] As described above, the solid tumor cancer may be selected from the group consisting of colorectal cancer, pancreatic cancer, primary liver cancer, renal cancer, ovarian cancer, uterine cancer, lung cancer, breast cancer, prostate cancer, sarcoma and cancer of adipose tissue.

[0035] In one embodiment, one or more of the following genes may be used as markers together with PTGR1 to determine sensitivity to irinoid anticancer agents: TNFRSF1B, LCK, TAL1, GNG12, S100A10, CD247, ATP1B1, LAMC1, PTPRC, PTPN7, PTPN14, CAPN2, ENAH, LCT, CXCR4, ITGA4, CASP10, HDAC4, NUP210, WWTR1, PFN2, MLF1, CD38, RHOH, ITK, LCP2, HIST1H3B, MYB, IKZF1, PIK3CG, MET, NRF1, TRBC1, PTPRN2, PTK2B, ASPH, NFIB, CNTRL, PRKCQ, MYOF, CTBP2, LM02, CD3D, TWF1, NCKAP1L, CKAP4, LCP1, CFL2, TJP1, ALDH1A2, TLE3, TNFRSF12A, PRKCB, NFATC3, WWOX, CBFA2T3, ATP2A3, GIPC1, HAUS5, MAP4K1, SDC4, APP, SLC38A5, WAS, and IL2RG.

[0036] In another embodiment, one or more of the following gene markers may be used: WWTR1, HIST1H3B, ASPH, MYOF, CTBP2, CBFA2T3, and SDC4. In another embodiment, one or more markers are combined with PTGR1 and combined with one, more, or all of the following genes: PTPN14, ITGA4, HDAC4, ITK, IKZF1, PIK3CG, NRF1, ASPH, and PRKCQ. In some embodiments, the sensitivity can approach 100%.

[0037] In yet another embodiment, two markers, PTGR1 and SDC4, may be used as markers.

[0038] When a gene combination of PTGR1 is used, screening for an anti-cancer drug sensitivity enhancer can be carried out by using, as an index, the variation in the expression of the gene combination of PTGR1 after exposure to an irinotecan-based anti-cancer drug. That is, in vitro or in vivo, a substance that reduces the PTGR1 gene combination level before exposure to an irinotecan-based anti-cancer drug, or a substance that promotes expression variation, or a substance that increases the level after exposure to an irinotecan-based anti-cancer drug enhances the sensitivity to the anti-cancer drug. In addition, in the case of in vitro, a substance that promotes expression variation, or a substance that increases the level after exposure to an anti-cancer drug corresponding to the target cancer cells can serve as a substance that enhances the sensitivity to an irinotecan-based anti-cancer drug (that is, an anti-cancer drug sensitivity enhancer).

[0039] To carry out a method for determining the sensitivity of a specimen to an anti-cancer drug, a kit including a protocol for measuring any of the substances present in the specimen is employed. The kit contains reagents for measuring any of these substances, instructions for use of the reagents, a standard for determining the presence or absence of sensitivity to an irinotecan-based anti-cancer drug, and the like. The standard includes the (relative) standard levels, (relative) high threshold levels, (relative) low threshold levels of these metabolism-related substances, factors affecting the measurement, and the degree of the effect. These substance levels may be set to be compatible with the selected irinotecan-based anti-cancer drug. The sensitivity determination may be carried out in the same manner based on the standard.

[0040] The screening of Irgin-based anticancer agents can be carried out using an Irgin-based anticancer agent sensitivity determination marker as an indicator. That is, a substance that can change the level of the anticancer agent sensitivity determination marker in vitro or in vivo is judged as an anticancer agent. For example, in the case of in vitro, in various cancer cells, a substance that changes the level of the anticancer agent sensitivity determination marker after exposure to the substance can play the role of an anticancer agent. Also, in a cancer-bearing animal, when the level of the anticancer agent sensitivity determination marker changes after administration of the substance to the animal, the substance can play the role of an anticancer agent. When it is predicted that the anticancer agent exhibits a pharmacological effect, an increase in the level of the anticancer agent sensitivity determination marker is observed before the occurrence of tumor shrinkage or the appearance of a cytotoxic effect. Therefore, screening based on the level of the anticancer agent sensitivity determination marker as an indicator can determine whether a test substance can play the role of a useful anticancer agent in a shorter period, and accordingly, it is predicted that the labor and cost involved in anticancer agent development will be significantly reduced.

[0041] If cancer is not sensitive to an anticancer agent, no pharmacological effect can be expected from the anticancer agent. If such an anticancer agent without a pharmacological effect continues to be administered to a patient, the cancer may progress and the side effects may worsen. Therefore, the anticancer agent sensitivity determination marker is not only adopted for the determination of the therapeutic response to the anticancer agent, but may also greatly contribute to the prevention of the worsening of side effects caused by the continuous administration of an anticancer agent without a pharmacological effect.

[0042] By combining and adopting the thus obtained Irgin-based anticancer agent sensitivity enhancer and the Irgin-based anticancer agent that is the target of sensitivity enhancement of the enhancer, the therapeutic effect of the Irgin-based anticancer agent is dramatically improved. The combination of the Irgin-based anticancer agent sensitivity enhancer and the anticancer agent that is the target of sensitivity enhancement of the enhancer may be a composition containing both components, or may be a combination drug of preparations containing the individual components.

[0043] If a reference value is obtained from a subject as part of an ongoing screening program, the monitoring of the subject is particularly supported. Alternatively, the reference value may be obtained from a population of subjects without solid tumor cancer.

[0044] Verification cells can be obtained by any method known in the art, including but not limited to during surgical resection, during biopsy such as needle biopsy, core biopsy, or aspiration, or collection from liquid samples such as blood, urine, cerebrospinal fluid, cyst fluid, etc. The methods for measuring DNA / mRNA include but are not limited to polymerase chain reaction, in situ hybridization, gel electrophoresis, sequence analysis, and microarray analysis, or combinations thereof. The methods for measuring proteins include but are not limited to mass spectrometry, 1-D or 2-D gel-based analysis systems, chromatography, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), enzyme immunoassay (EIA), Western blotting, immunoprecipitation, and immunohistochemistry. Antibody arrays or protein chips may be employed. In a subject, "high likelihood" of an anti-cancer effect being produced by an agent means that, in the verified parameters (e.g., mRNA of PTGR1, PTPN14, and ASPH, methylated DNA and / or protein, the expression levels of the genes or exons listed in Example 1, etc.), the subject is more similar to other subjects in whom the agent produces a significant anti-cancer effect than to other subjects in whom the agent does not produce a significant anti-cancer effect. In a subject, "low likelihood" of an anti-cancer effect being produced by an agent means that, in the verified parameters, the subject is more similar to other subjects in whom the agent does not produce a significant anti-cancer effect than to other subjects in whom the agent produces a significant anti-cancer effect.

[0045] The pharmaceutical composition can be used in formulations of individual single-unit dosage forms. The pharmaceutical compositions and dosage forms provided herein include the immunomodulatory compounds provided herein, or pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, or prodrugs thereof. The pharmaceutical compositions and dosage forms provided herein may further include one or more excipients.

[0046] The pharmaceutical compositions and dosage forms provided herein may also include one or more second active ingredients. As a result, the pharmaceutical compositions and dosage forms provided herein include the active ingredients (e.g., immunomodulatory compounds) disclosed herein. Examples of optimal second active ingredients or additional active ingredients are disclosed herein.

[0047] Kits and compositions for practicing the methods provided herein are also contemplated. In certain embodiments, kits useful for determining the efficacy of an anticancer compound are provided herein. In certain embodiments, kits useful for analyzing the efficacy of a compound in the treatment of a patient are provided herein. In some embodiments, kits useful for determining the effect of an immunomodulatory compound are provided herein. The kit includes a solid support and means for detecting the expression of the gene, protein, or glycoprotein of at least one biomarker in a biological sample. Such kits may employ, for example, urine test strips, membranes, chips, disks, test papers, filters, microspheres, slides, multiwell plates, or optical fibers. The solid support of the kit may be, for example, plastic, silicon, metal, resin, glass, membrane, particle, precipitate, gel, polymer, sheet, sphere, polysaccharide, capillary, film, plate, or slide. The biological sample may be, for example, a cell culture, cell line, tissue, oral tissue, gastrointestinal tissue, organ, intracellular organelle, biological fluid, blood sample, urine sample, or skin sample.

[0048] In one embodiment, the kit provided herein comprises an iridium compound provided herein, or a pharmaceutically acceptable salt, solvate, or hydrate thereof. The kit may further comprise additional active agents such as, but not limited to, the active agents disclosed herein.

Example

[0049] Certain embodiments provided herein are illustrated by the following non-limiting examples. As shown in Example 1, analysis of in vitro iridium (LP-184) sensitivity data from a panel of cancer cell lines with known multiomics molecular profiles revealed a signature of 10 genes (ASPH, HDAC4, IKZF1, ITGA4, ITK, NRF1, PIK3CG, PRKCQ, PTGR1, and PTPN14). These genes were able to predict iridium sensitivity with an accuracy of up to 100% in a blinded test. The gene expression, DNA mutation, DNA methylation, and protein expression status of these 10 genes were further computationally analyzed for correlation with iridium (LP-184) sensitivity. As shown in Table 1, it was revealed that 3 of these 10 genes had a significantly high correlation with the biological activity of iridium at the multiomics level. These genes are PTGR1, PTPN14, and ASPH. These 3 genes also had the highest gene weightings with respect to relative importance in determining iridium (LP-184) sensitivity in Figure 1. These 3 genes were found to be the most prominent genes when classifying samples as responders or non-responders to iridium as shown in Figure 2. In summary, a new gene set for determining sensitivity to and predicting response to iridium (LP-184) in cancer was established. Example 1

Table 1

Brief Description of the Drawings

[0050]

Figure 1

Figure 2

[0051] The above-described embodiments are intended to be merely illustrative, and those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific compounds, materials, and procedures. All such equivalents are considered to be within the scope of this embodiment and are encompassed by the appended claims.

Claims

**Claim 1** A method for treating solid tumor cancer using targeted drug therapy, comprising: identifying a patient having cancer that is sensitive to treatment with a compound of the following formula: 【Chemical 1】 wherein the method includes identifying a patient having cancer that is sensitive to treatment with a compound of the formula, wherein R1, R2, and R3 are independently (C1-C4) alkyl, methyl, or hydroxyl. **Claim 2** The method according to claim 1, further comprising the step of measuring the expression level of PTGR1 of the combination in a biological sample. **Claim 3** The method according to claim 1, further comprising the step of measuring the expression level of PTPN14 in a biological sample. **Claim 4** The method according to claim 1, further comprising the step of measuring the expression level of ASPH in a biological sample. **Claim 5** The method according to claim 1, wherein the cancer is newly diagnosed, recurrent, or refractory. **Claim 6** The method according to claim 1, further comprising modifying the targeted drug therapy based on gene expression. **Claim 7** The method according to claim 2, wherein PTGR1, PTPN14, or ASPH is methylated. **Claim 8** Ilzidine has the following structure: 【Chemical 2】 The method according to claim 1. **Claim 9** The method according to claim 1, wherein the cancer is colorectal cancer, pancreatic cancer, primary liver cancer, renal cancer, ovarian cancer, uterine cancer, lung cancer, breast cancer, prostate cancer, sarcoma, or cancer of adipose tissue. **Claim 10** A method for treating a solid tumor or managing solid tumor treatment, comprising: identifying a patient having solid tumor cancer that is sensitive to treatment with ilzidine having the following formula: 【Chemical Formula 3】 or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and administering to the patient a therapeutically effective amount of the ilzidine. **Claim 11** The method according to claim 10, wherein the biological sample is blood, plasma, serum, or a tissue biopsy. **Claim 12** The method according to claim 11, further comprising the step of measuring the expression level of PTGR1 in the biological sample. **Claim 13** The method according to claim 12, further comprising the step of measuring the expression level of PTPN14 in the biological sample. **Claim 14** The method according to claim 12, further comprising the step of measuring the expression level of ASPH in the biological sample. **Claim 15** A method for predicting the responsiveness to treatment in a patient having a solid tumor, comprising obtaining a biological sample from the patient, measuring the expression level of PTGR1, PTPN14, ASPH, or a combination thereof in the biological sample, and comparing the expression level in the biological sample with the expression level of a biological sample from a subject without solid cancer, wherein an increase in the expression level in the biological sample from the patient as compared to the level of the subject without the solid tumor indicates the likelihood of an effective response to treatment with a compound of the following formula: 【Chemical Formula 4】 A method showing the likelihood of an effective response to treatment with a compound of the formula, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

16. A kit for determining whether irudin may have an anti-cancer effect in cancer, comprising means for determining by comparing the level of PTGR1, PTPN14, ASPH, or a combination thereof in cancer with the normal value of a biological sample from a patient having a solid tumor.

17. The kit according to claim 16, wherein the cancer is colorectal cancer, pancreatic cancer, primary liver cancer, renal cancer, ovarian cancer, uterine cancer, lung cancer, breast cancer, prostate cancer, sarcoma, or cancer of adipose tissue.

18. A kit for determining whether irudin may have an anti-cancer effect in cancer, comprising means for determining the level of mRNA, DNA, and / or protein corresponding to PTGR1, PTPN14, ASPH, or a combination thereof in cancer cells.

19. The irudin is as follows: [Chemical Formula 5] The kit according to claim 16 or 18, having the following:

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