A Combinatorial Strategy for Targeting <i>BRAF</i> ^V600E-Mutant Cancers with BRAF^V600E Inhibitor (PLX4720) and Tyrosine Kinase Inhibitor (Ponatinib).

ABSTRACT:

Purpose

Most aggressive thyroid cancers are commonly associated with a BRAF ^V600E mutation. Preclinical and clinical data in BRAF ^V600E cancers suggest that combined BRAF and MEK inhibitor treatment results in a response, but resistance is common. One mechanism of acquired resistance is through persistent activation of tyrosine kinase (TK) signaling by alternate pathways. We hypothesized that combination therapy with BRAF and multitargeting TK inhibitors (MTKI) might be more effective in BRAF ^V600E thyroid cancer than in single-agent or BRAF and MEK inhibitors.

Experimental design

The combined drug activity was analyzed to predict any synergistic effect using high-throughput screening (HTS) of active drugs. We performed f

SUBMITTER: Ghosh C 

PROVIDER: S-EPMC8606228 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature