Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Cancer Manag Res. 2014 Oct 4;6:397-404. doi: 10.2147/CMAR.S37345. eCollection 2014.
MET receptor tyrosine kinase and its natural ligand, hepatocyte growth factor, have been implicated in a variety of cancers, including non-small cell lung cancer (NSCLC). Mechanisms by which cellular deregulation of MET occurs include overexpression, genomic amplification, mutation, or alternative splicing. MET overexpression or activation is a known cause of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in NSCLC. Inhibition of MET signaling in these EGFR tyrosine kinase inhibitor-resistant cells may potentially restore sensitivity to EGFR inhibitors. Tivantinib (ARQ 197), reported as a small-molecule MET inhibitor, has demonstrated antitumor activity in early clinical studies. This review focuses on MET and lung cancer, the clinical development of tivantinib, the clinical trials of tivantinib in NSCLC to date, its current/emerging role in the management of NSCLC, and future directions.
MET 受体酪氨酸激酶及其天然配体肝细胞生长因子已被牵涉到多种癌症中，包括非小细胞肺癌（NSCLC）。细胞 MET 失调的机制包括过表达、基因扩增、突变或选择性剪接。MET 过表达或激活是 NSCLC 中表皮生长因子受体（EGFR）酪氨酸激酶抑制剂获得性耐药的已知原因。抑制这些 EGFR 酪氨酸激酶抑制剂耐药细胞中的 MET 信号可能潜在恢复对 EGFR 抑制剂的敏感性。Tivantinib（ARQ 197），被报道为一种小分子 MET 抑制剂，在早期临床研究中显示出抗肿瘤活性。这篇综述重点介绍 MET 和肺癌、tivantinib 的临床开发、tivantinib 迄今为止在 NSCLC 中的临床试验、其在 NSCLC 管理中的当前/新兴作用以及未来方向。
