@article{a294b874ec444b45965ec78137954017,
title = "Beyond epidermal growth factor receptor: MET amplification as a general resistance driver to targeted therapy in oncogene-driven non-small-cell lung cancer",
abstract = "The rapidly changing treatment paradigm for patients with metastatic oncogene-driven lung cancer continues to evolve, and consequently our understanding of the landscape of resistance must also advance. MET amplification is an established and frequent driver of resistance in EGFR-mutant non-small-cell lung cancer (NSCLC). Recently, the combination of MET proto-oncogene (MET) and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has shown promise in overcoming this molecularly defined resistance in clinical trials, and this combination strategy is being pursued in ongoing trials. Emerging data also demonstrate MET amplification as a resistance driver to TKI-treated ALK-, RET-, and ROS-1-fusion NSCLC, consistently at the range of 15%, while the resistance profiling data are maturing for other molecular targets. In this review, we discuss MET amplification as a driver of acquired resistance in well-defined molecular subsets of NSCLC, explore the biology behind this mechanism of resistance, and summarize the recently published clinical data, including the proposed combination strategies in the clinic achieving success in overcoming acquired MET amplification-dependent resistance.",
keywords = "EGFR, MET, NSCLC, amplification, resistance, targeted therapy",
author = "N. Coleman and L. Hong and J. Zhang and J. Heymach and D. Hong and X. Le",
note = "Funding Information: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. XL is supported by Paul Calabresi Award at MDACC (K12/NIH), Rexanna's Foundation, Khalifa Scholarship, and Conquer Cancer Foundation; received research funds from Eli Lilly, Boehringer Ingelheim, and Spectrum Pharmaceuticals (all outside of the submitted work); received consultant and advisory fee from Eli Lilly, AstraZeneca, and EMD Serono (all outside of the submitted work). DH reports receiving consulting fees and research/grant funding from AbbVie, Adaptimmune, Adlai Nortye, Amgen, Astra-Zeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Eisai, Eli Lilly, EMD Serono, Erasca, Fate Therapeutics, Genentech, Genmab, GlaxoSmithKline, Ignyta, Infinity, Kite, Kyowa, LOXO, Merck, MedImmune, Millennium, Mirati, miRNA, Molecular Templates, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Seattle Genetics, Takeda, Turning Point Therapeutics, Verstatem, VM Oncology; travel, accommodations, and expenses covered by AACR, Amgen, ASCO, Astra Zeneca, Bayer, Celgene, Eli Lilly, Genentech, Genmab, GlaxoSmithKline, Janssen, LOXO, miRNA, Pfizer, Philips, SITC, Takeda; consulting, speaker, or advisory role with Alpha Insights, Acuta, Amgen, Axiom, Adaptimmune, Baxter, Bayer, Boxer Capital, COG, Ecor1, Genentech, GLG, Group H, Guidepoint, HCW Precision, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Prime Oncology, Seattle Genetics, ST Cube, Takeda, Tavistock, Trieza Therapeutics, and WebMD; other ownership interests in Molecular Match (Advisor), OncoResponse (Founder), and Presagia Inc (Advisor). JH reports advisory/consulting fees from Bristol-Myers Squibb, GlaxoSmithKline, Kairos Venture Investments, BrightPath Therapeutics, Hengrui Therapeutics, Eli Lilly, EMD Serono, and Foundation One Medicine, Spectrum, AstraZeneca; and research funding from NIH/NCI, American Cancer Society, Checkmate Pharmaceuticals, AstraZeneca, and Spectrum; and royalties and patents from Spectrum. JZ is supported by MD Anderson Physician Scientist Award (NIH R01), AACR Johnson and Johnson Innovative Cancer Research Award, Khalifa Scholarship, and Conquer Cancer Foundation; receives research funding from Merck and Johnson and Johnson; personal fees from AstraZeneca, Bristol-Myers Squibb, Geneplus-Beijing Institute, and InnoVent outside the submitted work. NC and LH have no disclosures. Funding Information: XL is supported by Paul Calabresi Award at MDACC (K12/NIH), Rexanna's Foundation, Khalifa Scholarship, and Conquer Cancer Foundation; received research funds from Eli Lilly, Boehringer Ingelheim, and Spectrum Pharmaceuticals (all outside of the submitted work); received consultant and advisory fee from Eli Lilly, AstraZeneca, and EMD Serono (all outside of the submitted work). DH reports receiving consulting fees and research/grant funding from AbbVie, Adaptimmune, Adlai Nortye, Amgen, Astra-Zeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Eisai, Eli Lilly, EMD Serono, Erasca, Fate Therapeutics, Genentech, Genmab, GlaxoSmithKline, Ignyta, Infinity, Kite, Kyowa, LOXO, Merck, MedImmune, Millennium, Mirati, miRNA, Molecular Templates, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Seattle Genetics, Takeda, Turning Point Therapeutics, Verstatem, VM Oncology; travel, accommodations, and expenses covered by AACR, Amgen, ASCO, Astra Zeneca, Bayer, Celgene, Eli Lilly, Genentech, Genmab, GlaxoSmithKline, Janssen, LOXO, miRNA, Pfizer, Philips, SITC, Takeda; consulting, speaker, or advisory role with Alpha Insights, Acuta, Amgen, Axiom, Adaptimmune, Baxter, Bayer, Boxer Capital, COG, Ecor1, Genentech, GLG, Group H, Guidepoint, HCW Precision, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Prime Oncology, Seattle Genetics, ST Cube, Takeda, Tavistock, Trieza Therapeutics, and WebMD; other ownership interests in Molecular Match (Advisor), OncoResponse (Founder), and Presagia Inc (Advisor). JH reports advisory/consulting fees from Bristol-Myers Squibb, GlaxoSmithKline, Kairos Venture Investments, BrightPath Therapeutics, Hengrui Therapeutics, Eli Lilly, EMD Serono, and Foundation One Medicine, Spectrum, AstraZeneca; and research funding from NIH/NCI, American Cancer Society, Checkmate Pharmaceuticals, AstraZeneca, and Spectrum; and royalties and patents from Spectrum. JZ is supported by MD Anderson Physician Scientist Award (NIH R01), AACR Johnson and Johnson Innovative Cancer Research Award, Khalifa Scholarship, and Conquer Cancer Foundation; receives research funding from Merck and Johnson and Johnson; personal fees from AstraZeneca, Bristol-Myers Squibb, Geneplus-Beijing Institute, and InnoVent outside the submitted work. NC and LH have no disclosures. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = dec,
doi = "10.1016/j.esmoop.2021.100319",
language = "English (US)",
volume = "6",
journal = "ESMO Open",
issn = "2059-7029",
publisher = "BMJ Publishing Group",
number = "6",
}