PIK3CA^H1047R-induced paradoxical ERK activation results in resistance to BRAF^V600E specific inhibitors in BRAF^V600E PIK3CA^H1047R double mutant thyroid tumors.

ABSTRACT: Thyroid carcinomas are the most prevalent endocrine cancers. The BRAF^V600E mutation is found in 40% of the papillary type and 25% of the anaplastic type. BRAF^V600E inhibitors have shown great success in melanoma but, they have been, to date, less successful in thyroid cancer. About 50% of anaplastic thyroid carcinomas present mutations/amplification of the phosphatidylinositol 3' kinase. Here we propose to investigate if the hyper activation of that pathway could influence the response to BRAF^V600E specific inhibitors. To test this, we used two mouse models of thyroid cancer. Single mutant (BRAF^V600E) mice responded to BRAF^V600E-specific inhibition (PLX-4720), while double mutant mice (BRAF^V600E; PIK3CA^H1047R) sho

SUBMITTER: Roelli MA 

PROVIDER: S-EPMC5732722 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature