BRAF-Mutated Advanced Colorectal Cancer: A Rapidly Changing Therapeutic Landscape.

Journal Article (Journal Article)

BRAF-mutated advanced colorectal cancer is a relatively small but critical subset of this tumor type on the basis of prognostic and predictive implications. BRAF alterations in colorectal cancer are classified into three functional categories on the basis of signaling mechanisms, with the class I BRAFV600E mutation occurring most frequently in colorectal cancer. Functional categorization of BRAF mutations in colorectal cancer demonstrates distinct mitogen-activated protein kinase pathway signaling. On the basis of recent clinical trials, current standard-of-care therapies for patients with BRAFV600E-mutated metastatic colorectal cancer include first-line cytotoxic chemotherapy plus bevacizumab and subsequent therapy with the BRAF inhibitor encorafenib and antiepidermal growth factor receptor antibody cetuximab. Treatment regimens currently under exploration in BRAFV600E-mutant metastatic colorectal cancer include combinatorial options of various pathway-targeted therapies, cytotoxic chemotherapy, and/or immune checkpoint blockade, among others. Circumvention of adaptive and acquired resistance to BRAF-targeted therapies is a significant challenge to be overcome in BRAF-mutated advanced colorectal cancer.

Full Text

Duke Authors

Cited Authors

  • Ciombor, KK; Strickler, JH; Bekaii-Saab, TS; Yaeger, R

Published Date

  • August 20, 2022

Published In

Volume / Issue

  • 40 / 24

Start / End Page

  • 2706 - 2715

PubMed ID

  • 35649231

Pubmed Central ID

  • PMC9390817

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.21.02541

Language

  • eng

Conference Location

  • United States