TY - JOUR
T1 - Managing Resistance to EFGR- and ALK-Targeted Therapies
AU - Lovly, Christine M.
AU - Iyengar, Puneeth
AU - Gainor, Justin F.
PY - 2017
Y1 - 2017
N2 - 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 resistance and strategies to overcome resistance among EGFR-mutant and ALK-rearranged lung cancers. To date, these strategies have centered on the development of novel next-generation inhibitors, rationale combinations, and use of local ablative therapies, such as radiotherapy.
AB - 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 resistance and strategies to overcome resistance among EGFR-mutant and ALK-rearranged lung cancers. To date, these strategies have centered on the development of novel next-generation inhibitors, rationale combinations, and use of local ablative therapies, such as radiotherapy.
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U2 - 10.14694/EDBK_176251
DO - 10.14694/EDBK_176251
M3 - Review article
C2 - 28561721
AN - SCOPUS:85039983013
SN - 1548-8756
VL - 37
SP - 607
EP - 618
JO - American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
JF - American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting
ER -