EGFR Mediates Responses to Small-Molecule Drugs Targeting Oncogenic Fusion Kinases.

ABSTRACT: Oncogenic kinase fusions of ALK, ROS1, RET, and NTRK1 act as drivers in human lung and other cancers. Residual tumor burden following treatment of ALK or ROS1⁺ lung cancer patients with oncogene-targeted therapy ultimately enables the emergence of drug-resistant clones, limiting the long-term effectiveness of these therapies. To determine the signaling mechanisms underlying incomplete tumor cell killing in oncogene-addicted cancer cells, we investigated the role of EGFR signaling in drug-naïve cancer cells harboring these oncogene fusions. We defined three distinct roles for EGFR in the response to oncogene-specific therapies. First, EGF-mediated activation of EGFR blunted fusion kinase inhibitor binding and restored fusion kinase signaling complexes.

SUBMITTER: Vaishnavi A 

PROVIDER: S-EPMC5516930 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature