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

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.