Novel biomarker for predicting sensitiviy to egfr-targeting agent, and use thereof

Abstract

The present disclosure relates to a new biomarker for predicting susceptibility to an EGFR-targeted agent and a use thereof, and more particularly, provides a biomarker for predicting susceptibility to an EGFR (Epidermal Growth Factor Receptor)-targeted agent, comprising a RON (Recepteur d' Origine Nantais) gene; a composition for predicting susceptibility to the EGFR-targeted agent, comprising an agent which measures a gene expression level of the biomarker; or an expression or activity level of a protein thereof; a composition for enhancing the susceptibility to the EGFR-targeted agent, comprising an inhibitor of the expression of the gene or the expression or activity of the protein of the gene as active ingredients; a kit for predicting the susceptibility to the EGFR-targeted agent, comprising the composition; and a method for predicting the susceptibility to the EGFR-targeted agent. According to the present disclosure, since an effect of predicting the susceptibility to the EGFR-targeted agent is excellent in a colon cancer, the present disclosure may be useful in the treatment of the colon cancer.

1 . A composition for predicting susceptibility to an epidermal growth factor receptor (EGFR)-targeted agent, the composition comprising an agent which measures an expression level of RON (recepteur d' origine nantais, Gene Bank accession No. NM_002447.1) gene; or an expression or activity level of a protein thereof. 
     
     
         2 . The composition of  claim 1 , wherein the composition further comprises an agent which measures an expression level of one or more genes selected from the group consisting of KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, Gene Bank accession No. NM_033360.2), NRAS (neuroblastoma RAS viral (v-ras) oncogene homolog, Gene Bank accession No. NP_002515.1), BRAF (v-raf murine sarcoma viral oncogene homolog B, Gene Bank accession No. NP_004324.2), EGFR (Epidermal Growth Factor Receptor, Gene Bank accession No. U48722.1), Adam11 (ADAM metallopeptidase domain 11, Gene Bank accession No. NM_002390.4), Adam32 (ADAM metallopeptidase domain 32, Gene Bank accession No. NM_145004.5), FZD4 (Frizzled family receptor 4, Gene Bank accession No. NM_012193.2), GPER (G protein-coupled estrogen receptor 1, NM_001505.2), and GPR101 (G protein-coupled receptor 101, Gene Bank accession No. NM_054021.1) genes; or an expression or activity level of a protein of the genes. 
     
     
         3 . The composition of  claim 2 , wherein the KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, Gene Bank accession No. NM_033360.2), NRAS (neuroblastoma RAS viral (v-ras) oncogene homolog, Gene Bank accession No. NP_002515.1), or BRAF (v-raf murine sarcoma viral oncogene homolog B, Gene Bank accession No. NP_004324.2) gene is a wild type. 
     
     
         4 . The composition of  claim 1 , wherein the EGFR-targeted agent is a therapeutic agent for one or more selected from the group consisting of adrenocorticotropic hormone (ACTH) produced tumors, acute lymphocytic or lymphoblastic leukemia, acute or chronic lymphocytic leukemia, acute non-lymphocytic leukemia, bladder cancer, brain tumors, breast cancer, cervix cancer, chronic myelogenous leukemia, lymphomas, endometriosis, esophagus cancer, bladder cancer, Ewing's sarcoma, tongue cancer, Hopkins lymphoma, Capo sheath sarcoma, kidney cancer, liver cancer, lung cancer, mesothelioma, multiple myeloma, neuroblastoma, non-hopkin lymphoma, osteosarcoma, ovarian cancer, lobular carcinoma, prostate cancer, pancreatic cancer, colorectal cancer, penis cancer, retinoblastoma, skin cancer, stomach cancer, thyroid cancer, uterine cancer, testicular cancer, wilms tumor, and trophoblastoma. 
     
     
         5 . The composition of  claim 1 , wherein the EGFR-targeted agent is one or more selected from the group consisting of cetuximab, gefitinib, erlotinib, panitumumab, PKI-166, EKB-569, HKI-272 (WAY-177820), icotinib, brigatinib, afatinib, lapatinib, canertinib, AEE788, XL647, and Zactima. 
     
     
         6 . The composition of  claim 1 , wherein the agent which measures the expression level of the gene comprises antisense oligonucleotide, a primer pair, or a probe which is specifically bound to mRNA of the gene. 
     
     
         7 . The composition of  claim 1 , wherein the agent which measures the expression or activity level of the protein comprises an antibody, a peptide, or a nucleotide which is specifically bound to the protein. 
     
     
         8 . The composition of  claim 1 , wherein when the expression level of the RON gene; or the expression or activity level of the protein thereof is low as compared with a normal level, it is determined that there is the susceptibility to the EGFR-targeted agent. 
     
     
         9 . The composition of  claim 1 , wherein when the expression level of the RON gene; or the expression or activity level of the protein thereof is high as compared with a normal level, it is determined that there is the resistance to the EGFR-targeted agent. 
     
     
         10 . A kit for predicting susceptibility to an EGFR (epidermal growth factor receptor)-targeted agent, the kit comprising the composition of  claim 1 .