Emerging MET tyrosine kinase inhibitors for the treatment of non-small cell lung cancer.

Emerging MET tyrosine kinase inhibitors for the treatment of non-small cell lung cancer. Expert Opin Emerg Drugs. 2020 Jul 02;: Authors: Fujino T, Suda K, Mitsudomi T Abstract INTRODUCTION: MET aberrations, including MET exon 14 skipping mutation and amplification, are present in ~5% of non-small cell lung cancer (NSCLC) cases, and these levels are comparable to the frequency of ALK fusion. MET amplification also occurs as an acquired resistance mechanism in EGFR-mutated NSCLC after EGFR tyrosine kinase inhibitors (TKI) treatment failure. Therefore, the development of therapies for activated MET is urgently needed. AREAS COVERED: This review summarizes (1) the mechanisms and frequencies of MET aberrations in NSCLC, (2) the efficacies and toxicities of MET-TKIs under clinical development and (3) the mechanisms of inherent and acquired resistance to MET-TKIs. EXPERT OPINION: Type Ia, Ib and II MET-TKIs are currently under clinical development, and phase I/II studies have shown the potent activities of tepotinib, capmatinib and savolitinib; in fact, tepotinib and capmatinib are expected to soon be approved for use by health authorities. However, inherent and acquired resistance through on- and off-target mechanisms has been detected, and strategies to overcome this resistance are being developed. PMID: 32615820 [PubMed - as supplied by publisher]
Source: Expert Opinion on Emerging Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Emerg Drugs Source Type: research