BCL-X_L inhibitors enhance the apoptotic efficacy of BRAF inhibitors in BRAF^V600E colorectal cancer.

ABSTRACT: Metastatic BRAF^V600E colorectal cancer (CRC) carries an extremely poor prognosis and is in urgent need of effective new treatments. While the BRAF^V600E inhibitor encorafenib in combination with the EGFR inhibitor cetuximab (Enc+Cet) was recently approved for this indication, overall survival is only increased by 3.6 months and objective responses are observed in only 20% of patients. We have found that a limitation of Enc+Cet treatment is the failure to efficiently induce apoptosis in BRAF^V600E CRCs, despite inducing expression of the pro-apoptotic protein BIM and repressing expression of the pro-survival protein MCL-1. Here, we show that BRAF^V600E CRCs express high basal levels of the pro-survival proteins MCL-1 and BCL-X_L, and that c

SUBMITTER: Jenkins LJ 

PROVIDER: S-EPMC10907349 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature