Targeting BRAF aberrations in advanced colorectal carcinoma: from bench to bedside

Future Oncol. 2016 Jan;12(1):25-30. doi: 10.2217/fon.15.226. Epub 2015 Nov 30.

Abstract

Colorectal cancer (CRC) is a global health problem with profound mortality and morbidity effects particularly in the advanced/metastatic setting. Because of the recent understanding of the biology of this disease, many candidate targets have come into light for therapeutic evaluation. The current review is about evaluating the preclinical and clinical aspects of BRAF as a therapeutic target in this disease. The available clinical results suggest that while the use of unselective RAF inhibitors (e.g., sorafenib) has been ineffective in the management of advanced CRC patients with KRAS mutation, combination of selective BRAF inhibitors plus EGFR inhibitors may represent a good therapeutic strategy in BRAF-mutant CRC.

Keywords: BRAF; colon cancer; dabrafenib; vemurafenib.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Humans
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasm Staging
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Sorafenib

Substances

  • KRAS protein, human
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib
  • EGFR protein, human
  • ErbB Receptors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)