New advances in the clinical management of RAS and BRAF mutant colorectal cancer patients

Expert Rev Gastroenterol Hepatol. 2021 Jan;15(1):65-79. doi: 10.1080/17474124.2021.1826305. Epub 2020 Oct 12.

Abstract

Introduction: In colorectal carcinogenesis, genetic alterations in RAS and BRAF oncogenes play an important role for cancer initiation and/or progression and represent a key focus in the search for targeted therapies. Despite many years of research and a great amount of studies, until very recently this pathway was considered extremely hard to downregulate to obtain a significant clinical impact in colorectal cancer patients. But better times are coming with the advent of new promising drugs and combinations strategies.

Areas covered: In this review, we go over the biological characteristics of the MAPK pathway in colorectal tumors, while illustrating the clinical correlation of RAS and BRAF mutations, particularly its prognostic and predictive value. We also present newly data about recent improvements in the treatment strategy for patients harboring these types of tumors.

Expert commentary: With great advances in the knowledge of molecular basis of RAS and BRAF mutant colorectal cancer in conjunction with biotechnology development and the constant effort for improvement, in the near future many new therapeutic options would be available for the management of this group of patient with dismal prognosis.

Keywords: Colorectal cancer; braf; egfr; mapk; mek; ras; targeted therapy.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Genes, ras / drug effects
  • Genes, ras / genetics*
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / drug effects
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mutation
  • Oncogenes / drug effects
  • Oncogenes / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / drug effects
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinase Kinases