Long-term vemurafenib treatment drives inhibitor resistance through a spontaneous KRAS G12D mutation in a BRAF V600E papillary thyroid carcinoma model.

ABSTRACT: The BRAF V600E mutation is commonly observed in papillary thyroid cancer (PTC) and predominantly activates the MAPK pathway. Presence of BRAF V600E predicts increasing risk of recurrence and higher mortality rate, and treatment options for such patients are limited. Vemurafenib, a BRAF V600E inhibitor, is initially effective, but cells inevitably develop alternative mechanisms of pathway activation. Mechanisms of primary resistance have been described in short-term cultures of PTC cells; however, mechanisms of acquired resistance have not. In the present study, we investigated possible adaptive mechanisms of BRAF V600E inhibitor resistance in KTC1 thyroid cancer cells following long-term vemurafenib exposure. We found that a subpopulation of KTC1 cells acquired resistance to vemurafenib fo

SUBMITTER: Danysh BP 

PROVIDER: S-EPMC5058727 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature