MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer

Treatment of non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutation with EGFR-TKIs has achieved great success, yet faces the development of acquired resistance as the major obstacle to long-term disease remission in the clinic. MET (or c-MET ) gene a...

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Bibliographic Details
Published in:Journal of hematology and oncology Vol. 12; no. 1; pp. 63 - 11
Main Authors: Wang, Qiming, Yang, Sen, Wang, Kai, Sun, Shi-Yong
Format: Journal Article
Language:English
Published: London BioMed Central 21.06.2019
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects:
Acrylamides - pharmacology
Acrylamides - therapeutic use
Aniline Compounds - pharmacology
Aniline Compounds - therapeutic use
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cancer Research
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Development and progression
Drug Resistance, Neoplasm
Drug therapy
Emerging agents and regimens for cancer therapy
Epidermal growth factor
Epidermal growth factor receptors
ErbB Receptors - antagonists & inhibitors
ErbB Receptors - genetics
Gene amplification
Gene expression
Genetic aspects
Hematology
Humans
Immunotherapy
Kinases
Ligands
Lung cancer
Lung cancer, Non-small cell
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Medicine
Medicine & Public Health
MEK inhibitors
Molecular Targeted Therapy
Mutation
Non-small cell lung carcinoma
Oncology
Phosphorylation
Physiological aspects
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Proteins
Proto-Oncogene Proteins c-met - antagonists & inhibitors
Proto-Oncogene Proteins c-met - genetics
Remission
Review
Targeted cancer therapy
China
ISSN:1756-8722, 1756-8722
Online Access:Get full text
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Description
Summary:Treatment of non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutation with EGFR-TKIs has achieved great success, yet faces the development of acquired resistance as the major obstacle to long-term disease remission in the clinic. MET (or c-MET ) gene amplification has long been known as an important resistance mechanism to first- or second-generation EGFR-TKIs in addition to the appearance of T790 M mutation. Recent preclinical and clinical studies have suggested that MET amplification and/or protein hyperactivation is likely to be a key mechanism underlying acquired resistance to third-generation EGFR-TKIs such as osimertinib as well, particularly when used as a first-line therapy. EGFR-mutant NSCLCs that have relapsed from first-generation EGFR-TKI treatment and have MET amplification and/or protein hyperactivation should be insensitive to osimertinib monotherapy. Therefore, combinatorial therapy with osimertinib and a MET or even a MEK inhibitor should be considered for these patients with resistant NSCLC carrying MET amplification and/or protein hyperactivation.
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ISSN:1756-8722
1756-8722
DOI:10.1186/s13045-019-0759-9