Forty‐nine gastric cancer cell lines with integrative genomic profiling for development of c‐MET inhibitor. Issue 1 (23rd February 2018)

• Record Type: Journal Article
• Authors: Kim, Hyun Jeong; Kang, Sun Kyoung; Kwon, Woo Sun; Kim, Tae Soo; Jeong, Inhye; Jeung, Hei‐Cheul; Kragh, Michael; Horak, Ivan D.; Chung, Hyun Cheol; Rha, Sun Young
• Is Part Of: International journal of cancer. Volume 143:Issue 1(2018)
• Page Start: 151
• Page End: 159
• Publication Date: 2018-02-23
• Subjects: gastric cancer -- cell line -- MET -- HGF -- targeted therapy; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31304
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Receptor tyrosine kinase MET (c‐MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c‐MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET ‐related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty‐nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET ‐related molecules. Four c‐MET inhibitors were tested to elucidate the dependency on MET pathway in the 49 GC cell lines. Six of 49 cell lines were MET amplified with overexpression of c‐MET and p‐MET. The variants of MET were not associated with c‐MET expression or amplification. Hs746T showed an exon 14 deletion in conjunction with MET amplification. The cell lines were divided into 6 MET amplified, 2 c‐MET overexpressed, 2 hepatocyte growth factor (HGF) overexpressed, and 39 MET ‐negative subgroups. Except tivantinib, the c‐MET inhibitors showed higher inhibition (%) in MET amplified than in MET nonamplified cell lines that MET amplified cell lines showed MET pathway dependency. However, the c‐MET overexpressed and HGF overexpressed cell lines showed moderate dependency on MET pathway. Well‐characterized cell lines are very important in studying drug development. Our 49 GC cell lines had various characteristics of MET and MET ‐related molecules and MET pathway dependency. These provide a promising platform for development of various RTK inhibitors including c‐MET inhibitors. Abstract : What's new? The tyrosine receptor kinase MET has been identified as a potential target for gastric cancer therapy. Here the authors performed a detailed analysis of 49 gastric cancer cell lines for genomic MET status and responsiveness to MET‐related pathway drugs. They identified 10 cell lines with MET‐associated abnormalities, which could be of value for future research of MET biology and MET‐associated therapeutics in gastric cancer.