Original ArticleTranslational OncologyRET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies
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Drs. Solomon, Tan, Lin, Wong, and Hollizeck equally contributed to this work.
Disclosure: Dr. Solomon reports personal fees and other from Loxo Oncology, during the conduct of the study; personal fees from Novartis, Pfizer, Roche-Genentech, AstraZeneca, Merck & Co., Bristol-Myers Squibb, and Gritstone Oncology, outside the submitted work, Dr. Lin reports other from Pfizer, C4 Therapeutics, Novartis, Hengrui, Turning Point Therapeutics, Neon Therapeutics, Nuvalent, OncLive, and MedScape, outside the submitted work; Dr. Ebata reports other from Loxo Oncology, during the conduct of the study; Dr. Tuch reports other from Loxo Oncology, during the conduct of the study; Dr. Yoda reports grants from Lung Cancer Research Foundation, during the conduct of the study; Dr. Gainor reports personal fees from Bristol-Myers Squibb, Genentech-Roche, Takeda, Loxo Oncology-Eli Lilly, Pfizer, Incyte, Novartis, Merck & Co., Agios, Amgen, Regeneron, Oncorus, Array, and Jounce; and other from Ironwood Pharmaceuticals, outside the submitted work; Dr. Sequist reports grants from Loxo Oncology, during the conduct of the study; grants and personal fees from AstraZeneca, Merrimack Pharmaceuticals and Blueprint Medicines; grants from Novartis, Genentech, and Boehringer Ingelheim; and personal fees from Janssen, outside the submitted work; Dr. Oxnard reports personal fees from Loxo Oncology, AstraZeneca, Janssen, AbbVie, Foundation Medicine, Inivata, Illumina, Blueprint Medicines, Takeda, and Guardant, outside the submitted work.; Dr. Drilon reports other from Ignyta/Genentech/Roche, Eli Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui, Exelixis, Tyra, Verastem, MORE Health, AbbVie, and Loxo Oncology/Bayer, outside the submitted work, and Associated Research Paid to Institution (Pfizer, Exelixis, GlaxoSmithKlein, Teva, Taiho, PharmaMar), Research (Foundation Medicine), Royalties (Wolters Kluwer), Other (Merck/Puma), and CME Honoraria (Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Oncology); Dr. Subbiah reports grants from Loxo Oncology/Eli Lilly, Novartis, GlaxoSmithKline, during the conduct of the study; grants from Bayer, Nano Carrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, Pharmamar, D3, Pfizer Multivir, Amgen, AbbVie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, and Blueprint Medicines, outside the submitted work; and travel support from Novartis, Pharmamar, American Society for Clinical Oncology, European Society for Clinical Oncology, Helsin, and Incyte; Dr. Zhu reports other from Loxo Oncology, outside the submitted work; Dr. Nguyen reports other from Loxo Oncology, outside the submitted work; Ms. Henry reports other from Loxo Oncology, outside the submitted work; Dr. Condroski reports other from Loxo Oncology, outside the submitted work; Ms. Kolakowski reports other from Loxo Oncology and Array BioPharma, outside the submitted work. In addition, Ms. Kolakowski has three patents issued: WO2018071447, WO2019075092, and WO2019075108; Dr. Gomez reports other from Loxo Oncology, outside the submitted work; Mr. Ballard reports other from Loxo Oncology, outside the submitted work; Mr. Metcalf reports other from Loxo Oncology and Array BioPharma, outside the submitted work. In addition, Mr. Metcalf has three patents issued: WO2018071447, WO2019075092, and WO2019075108; Dr. Dawson reports grants from Genentech and Pfizer, outside the submitted work; Dr. Stancato reports other from Eli Lilly, outside the submitted work; Dr. Brandhuber reports employment at Loxo Oncology and previous equity in Loxo Oncology; Dr. Andrews reports other from Loxo Oncology and Array BioPharma, outside the submitted work. In addition, Dr. Andrews has three patents issued: WO2018071447, WO2019075092, and WO2019075108; Dr. Robinson reports personal fees from Loxo Oncology, during the conduct of the study, personal fees from Eisai, outside the submitted work; Dr. Rothenberg reports other from Loxo Oncology, outside the submitted work. The remaining authors declare no conflict of interest.