RNF43 mutations predict response to anti-BRAF/EGFR combinatory therapies in BRAF^V600E metastatic colorectal cancer.

ABSTRACT: Anti-BRAF/EGFR therapy was recently approved for the treatment of metastatic BRAF^V600E colorectal cancer (mCRC^BRAF-V600E). However, a large fraction of patients do not respond, underscoring the need to identify molecular determinants of treatment response. Using whole-exome sequencing in a discovery cohort of patients with mCRC^BRAF-V600E treated with anti-BRAF/EGFR therapy, we found that inactivating mutations in RNF43, a negative regulator of WNT, predict improved response rates and survival outcomes in patients with microsatellite-stable (MSS) tumors. Analysis of an independent validation cohort confirmed the relevance of RNF43 mutations to predicting clinical benefit (72.7% versus 30.8%; P = 0.03), as well as longer progression-free survival (hazard rati

SUBMITTER: Elez E 

PROVIDER: S-EPMC9556333 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature