Journal article
RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies
BJ Solomon, L Tan, JJ Lin, SQ Wong, S Hollizeck, K Ebata, BB Tuch, S Yoda, JF Gainor, LV Sequist, GR Oxnard, O Gautschi, A Drilon, V Subbiah, C Khoo, EY Zhu, M Nguyen, D Henry, KR Condroski, GR Kolakowski Show all
Journal of Thoracic Oncology | ELSEVIER SCIENCE INC | Published : 2020
Abstract
Introduction: Novel rearranged in transfection (RET)-specific tyrosine kinase inhibitors (TKIs) such as selpercatinib (LOXO-292) have shown unprecedented efficacy in tumors positive for RET fusions or mutations, notably RET fusion-positive NSCLC and RET-mutated medullary thyroid cancer (MTC). However, the mechanisms of resistance to these agents have not yet been described. Methods: Analysis was performed of circulating tumor DNA and tissue in patients with RET fusion-positive NSCLC and RET-mutation positive MTC who developed disease progression after an initial response to selpercatinib. Acquired resistance was modeled preclinically using a CCDC6-RET fusion-positive NSCLC patient-derived xe..
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Awarded by National Cancer Institute
Funding Acknowledgements
This study was supported by Loxo Oncology, Inc., and by a donation from the Costello family to the Peter MacCallum Cancer Centre Foundation. BJS was supported by a National Health and Medical Research Investigator grant.