医学
酪氨酸激酶
后天抵抗
癌症研究
肺癌
机制(生物学)
克里唑蒂尼
癌症
内科学
肿瘤科
受体
认识论
哲学
恶性胸腔积液
作者
Toshio Fujino,Kenichi Suda,Tetsuya Mitsudomi
标识
DOI:10.1080/14728214.2020.1791821
摘要
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 were 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.
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