title: Attacking a Moving Target: Understanding Resistance and Managing Progression in EGFR-Positive Lung Cancer Patients Treated With Tyrosine Kinase Inhibitors.
abstract: Multiple randomized studies have demonstrated improved response rates, progression-free survival, and quality of life for treatment-naive, advanced-stage adenocarcinoma patients harboring sensitizing EGFR mutations when they are treated with tyrosine kinase inhibitor therapy, as compared with chemotherapy. Despite improved outcomes with these agents, the majority of patients will eventually develop resistance and subsequent clinical progression. Recently, there has been a firmer understanding of the molecular mechanisms of the resistance that develops as a consequence of treatment, most notably the identification of a second-site EGFR mutation, T790M. While this understanding can inform subsequent treatment decisions, disease progression can be heterogeneous, and there are several competing therapeutic options. Treatment decisions must consider this clinical heterogeneity, factoring in the pace of disease growth, lung cancer-related symptoms, and the potential presence of T790M mutations. Herein, we review the available literature addressing these competing strategies and attempt to clarify best treatment practices, including the emerging role of T790M-directed therapies.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Levy
authors.forename: Parth
authors.initials: P
authors.lastname: Rao
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Becker
authors.forename: Kevin
authors.initials: K
authors.lastname: Becker
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases