MET/HGF pathway activation as a paradigm of resistance to targeted therapies

Annals of Translational Medicine
Brian KoBalazs Halmos

Abstract

Resistance to targeted therapeutics is a key issue limiting the long-term utility of these medications in the management of molecularly selected subsets of cancer patients, including patients with non-small cell lung cancer harboring oncogenic alterations affecting EGFR, ALK and other genes. Bypass resistance mediated by activation of MET kinase has emerged as a frequent, validated and pivotal resistance mechanism in multiple types of cancers. Biochemical understanding is accumulating to explain the unique role of MET in such bypass pathways, providing alternate downstream activation opportunities and intricate interactions during epithelial-mesenchymal transitions. Multiple diagnostic testing platforms have become available for selecting appropriate patients for MET targeting in a variety of settings. Importantly, in light of the failures of several earlier clinical studies of MET targeting agents, a large array of recent and current MET-focused trials are incorporating stricter patient selection and more robust predictive biomarkers providing hope for validation of MET targeting as a clinically impactful strategy.

Citations

Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Alberto PucciniFrancesca Battaglin
Apr 5, 2019·Future Medicinal Chemistry·Vishnu C Damalanka, James W Janetka
May 1, 2019·Journal of Cellular Biochemistry·Showket HussainRavi Mehrotra
Feb 13, 2020·Frontiers in Genetics·Shivapriya JeyaramanNadiah Abu
Feb 3, 2021·Oncogene·Georgina E WoodStéphanie Kermorgant
May 5, 2021·Expert Opinion on Therapeutic Targets·Matthew LeeBalazs Halmos
Dec 21, 2018·Journal of Medicinal Chemistry·Vishnu C DamalankaJames W Janetka
Mar 3, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fernanda Marconi RoversiJoão Agostinho Machado-Neto

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