Vemurafenib-resistance via de novo RBM genes mutations and chromosome 5 aberrations is overcome by combined therapy with palbociclib in thyroid carcinoma with BRAF^V600E.

ABSTRACT:

Purpose

Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF^V600E represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF^WT/V600E-positive PTC patient-derived cells with P16^-/- (CDKN2A^-/-).

Experimental design

Following treatment with vemurafenib, we expanded a sub-population of cells with primary resistance and characterized them genetically and cytogenetically. We have

SUBMITTER: Antonello ZA 

PROVIDER: S-EPMC5689570 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature