Method for predicting efficacy of c-Met inhibitor
A biomarker for predicting and/or monitoring the efficacy of a c-Met inhibitor; a composition for predicting and/or monitoring the efficacy of a c-Met inhibitor, comprising a material detecting the biomarker; a composition for selecting a subject suitable for the application of a c-Met inhibitor, comprising a material detecting the biomarker; a method for predicting and/or monitoring the efficacy of a c-Met inhibitor using the biomarker; a method for selecting a subject suitable for the application of a c-Met inhibitor using the biomarker; and a method for preventing and/or treating cancer comprising administering a c-Met inhibitor to the selected subject.
1. A method for selecting a subject suitable for the application of a c-Met inhibitor in cancer treatment, comprising:
measuring the level of IL-8 in a serum sample from a patient having cancer;
determining the presence of K-RAS and B-RAF mutations in a cancer tissue sample from the patient having cancer;
measuring the level of c-Met expression in a cancer tissue sample from the patient having cancer;
selecting the patient as the subject suitable for the application of a c-Met inhibitor when the level of IL-8 in the serum sample is about 500 pg/ml or higher, no K-RAS or B-RAF mutations are found in the cancer tissue sample, and c-Met is expressed in the cancer tissue sample; and
administering the c-Met inhibitor to the selected patient.
2. The method of claim 1 , wherein measuring the level of IL-8 comprises contacting the serum sample with an antibody or antigen-binding fragment thereof that specifically binds to IL-8.
3. The method of claim 2 , wherein the antibody or antigen-binding fragment thereof that specifically binds to IL-8 is at least one selected from the group consisting of scFv, (scFv)2, scFv-Fc, Fab, Fab′, and F(ab′)2.
4. The method of claim 1 , wherein the c-Met inhibitor is at least one selected from the group consisting of an anti-c-Met antibody or an antigen-binding fragment thereof, crizotinib, cabozantinib, foretinib, PHA-665752, SU11274, SGX-523, PF-04217903, EMD 1214063, golvatinib, INCB28060, MK-2461, tivantinib, NVP-BVU972, AMG458, BMS 794833, BMS 777607, MGCD-265, AMG-208, BMS-754807, JNJ-38877605, pharmaceutically acceptable salts thereof, rilotumumab, and combinations thereof, wherein the anti-c-Met antibody is selected from the group consisting of (1) an antibody recognizing or binding to a polypeptide comprising 5 to 19 contiguous amino acid residues within SEQ ID NO: 71 and wherein the polypeptide comprises at least SEQ ID NO: 73, (2) onartuzumab, and (3) LY2875358.
5. The method of claim 4 , wherein the c-Met inhibitor comprises an anti-c-Met antibody or an antigen-binding fragment thereof that comprises: (a) a CDR-H1 comprising SEQ ID NO: 1, 22, 23, or 24; (b) a CDR-H2 comprising SEQ ID NO: 2, 25, or 26; (c) a CDR-H3 comprising SEQ ID NO: 3, 27, 28, or 85; (d) a CDR-L1 comprising SEQ ID NO: 10, 29, 30, 31, 32, 33, or 106, (e) a CDR-L2 comprising SEQ ID NO: 11, 34, 35, or 36, and (f) a CDR-L3 comprising SEQ ID NO: 12, 13, 14, 15, 16, 37, 86, or 89.
6. The method of claim 4 , wherein the c-Met inhibitor comprises an anti-c-Met antibody or an antigen-binding fragment thereof that comprises: (a) a CDR-H1 comprising SEQ ID NO: 1; (b) a CDR-H2 comprising SEQ ID NO: 2; (c) a CDR-H3 comprising SEQ ID NO: 3; (d) a CDR-L1 comprising SEQ ID NO: 10, (e) a CDR-L2 comprising SEQ ID NO: 11, and (f) a CDR-L3 comprising SEQ ID NO: 12, 13, 14, 15, or 16.