The Unfolded Protein Response: A Novel Therapeutic Target for Poor Prognostic <i>BRAF</i> Mutant Colorectal Cancer.

ABSTRACT: BRAF^V600E mutations occur in ∼10% of colorectal cancer cases, are associated with poor survival, and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition. There is an unmet need to understand the biology of poor prognostic BRAFMT colorectal cancer. We have used differential gene expression and pathway analyses of untreated stage II and stage III BRAFMT (discovery set: n = 31; validation set: n = 26) colorectal cancer, and an siRNA screen to characterize the biology underpinning the BRAFMT subgroup with poorest outcome. These analyses identified the unfolded protein response (UPR) as a novel and druggable pathway associated with the BRAFMT colorectal cancer subgroup with poorest outcome. We also found that

SUBMITTER: Forsythe N 

PROVIDER: S-EPMC5985931 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature