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MET Oncogene in Non-Small Cell Lung Cancer: Mechanism of MET Dysregulation and Agents Targeting the HGF/c-Met Axis

Authors Liang H, Wang M

Received 16 September 2019

Accepted for publication 16 February 2020

Published 25 March 2020 Volume 2020:13 Pages 2491—2510


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche

Hongge Liang, Mengzhao Wang

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, People’s Republic of China

Correspondence: Mengzhao Wang
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, People’s Republic of China
Tel +86 10-69155039

Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide and has a poor prognosis. Current treatments for advanced NSCLC included traditional chemotherapy, radiotherapy, targeted therapy, and immunotherapy. The efficacy of targeted therapy relies on oncogene addiction. Mesenchymal-epithelial transition factor (MET) gene can encode unconventional receptor tyrosine kinases with pleiotropic functions, when signals are abnormally activated, it can initiate and maintain tumor transformation, promote cell proliferation, survival, tumor invasion and angiogenesis. Thus, it is a promising therapeutic target. Previous studies have shown that elevated levels of HGF and/or overexpression of c-Met are associated with poor prognosis in lung cancer. In preclinical and clinical trials, c-MET inhibitors have shown some antitumor activity in NSCLC. Although the efficacy results of MET inhibitors in Phase III clinical trials are disappointing, given the molecular heterogeneity of NSCLC, only subgroups of patients with MET gene alterations may benefit from c-MET inhibitors. The challenge for the future is to screen out the potential beneficiaries. To solve this problem, there is need for large data analysis for the detection methods and treatment effects, to establish standards that meet the MET activation status, and determine reliable thresholds to achieve effective patient stratification and clinical decision making. This article summarized the structure of the hepatocyte growth factor (HGF)/c-Met axis, the different mechanisms of MET addiction, as well as MET amplification as acquired resistance mechanism to epidermal growth factor receptor-tyrosine kinase inhibitors, the latest advances of MET inhibitors, and immuotherapy in the treatment of NSCLC with MET alterations.

Keywords: c-mesenchymal-epithelial transition, receptor tyrosine kinases, non-small cell lung cancer, treatment, oncogene addiction

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