Preclinical Activity of the Type II RAF Inhibitor Tovorafenib in Tumor Models Harboring Either a BRAF Fusion or an NF1 Loss-of-Function Mutation.

ABSTRACT:

Abstract

Genomic alterations and dysregulation of the MAPK pathway have been described in many different types of cancers. BRAFV600 mutations and BRAF fusions, found in both pediatric and adult cancers, are oncogenic drivers that drive constitutive activation of the RAF pathway. Neurofibromin 1 (NF1) loss-of-function (LOF) mutations, which occur in many cancer types, result in decreased neurofibromin GAP function, thus activating RAS. Tovorafenib is an oral selective, central nervous system–penetrant, type II RAF inhibitor which inhibits RAF monomers and dimers. In this study, the impact of tovorafenib alone or in combination with MEK inhibitor, pimasertib, was explored in adult or pediatric tumor models harboring BRAF fusions or NF1-LOF mutations. Tovorafenib resulted in tumor reg

SUBMITTER: Rastogi S 

PROVIDER: S-EPMC12015663 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature