biostudies-literatureLovly CMNCI NIH HHS607-618https://www.ebi.ac.uk/biostudies/studies/S-EPMC10183098biostudies-literatureUnknown37Targeted therapies have transformed the management of non-small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors. In this review, we present a framework for understanding resistance to targeted therapies. We also provide overviews of the molecular mechanisms of resistanceAmerican Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual MeetingManaging Resistance to EFGR- and ALK-Targeted Therapies.PMC10183098K12 CA090625Lovly CMIyengar PGainor JFfalseManaging Resistance to EFGR- and ALK-Targeted Therapies.Targeted therapies have transformed the management of non-small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors. In this review, we present a framework for understanding resistance to targeted therapies. We also provide overviews of the molecular mechanisms of resistance2017-01-01T00:00:00Z20172025-04-04T13:07:27.878Z2025-04-04T13:07:27.878ZS-EPMC101830982856172110.1200/edbk_17625110.1200/EDBK_176251