Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398.

ABSTRACT: Activation of FGFR signaling through mutations, amplifications, or fusions involving FGFR1, 2, 3, or 4 is seen in multiple tumors, including lung, bladder, and cholangiocarcinoma. Currently, several clinical trials are evaluating the role of novel FGFR inhibitors in solid tumors. As we move forward with FGFR inhibitors clinically, we anticipate the emergence of resistance with treatment. Consequently, we sought to study the mechanism(s) of acquired resistance to FGFR inhibitors using annotated cancer cell lines. We identified cancer cell lines that have activating mutations in FGFR1, 2, or 3 and treated them chronically with the selective FGFR inhibitor, BGJ398. We observed resistance to chronic BGJ398 exposure in DMS114 (small-cell lung cancer, FGFR1 amp

SUBMITTER: Datta J 

PROVIDER: S-EPMC5539948 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature