Combination <i>BRAF^V600E</i> Inhibition with the Multitargeting Tyrosine Kinase Inhibitor Axitinib Shows Additive Anticancer Activity in <i>BRAF^V600E</i>-Mutant Anaplastic Thyroid Cancer.

ABSTRACT: Background: Anaplastic thyroid cancer (ATC) is uniformly lethal. BRAF^V600E mutation is present in 45% of patients with ATC. Targeted therapy with combined BRAF and MEK inhibition in BRAF^V600E-mutant ATC can be effective, but acquired resistance is common because this combination targets the same pathway. Drug matrix screening, in BRAF^V600E ATC cells, of highly active compounds in combination with BRAF inhibition showed multitargeting tyrosine kinase inhibitors (MTKIs) had the highest synergistic/additive activity. Thus, we hypothesized that the combination of BRAF^V600E inhibition and an MTKI is more effective than a single drug or combined BRAF and MEK inhibition in BRAF^V600E-mutant ATC.

SUBMITTER: Gunda V 

PROVIDER: S-EPMC10625471 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature