Targeting the serrated pathway of colorectal cancer with mutation in BRAF

Biochim Biophys Acta. 2016 Aug;1866(1):51-63. doi: 10.1016/j.bbcan.2016.06.003. Epub 2016 Jun 21.

Abstract

A recently acknowledged morphological pathway to colorectal cancer originates from precursor polyps with a serrated appearance due to branching and folding of the colon epithelium. This serrated origin accounts for up to 30% of all colorectal tumors but these are heterogeneous regarding molecular characteristics and patient outcome. Here we review the current knowledge about the classification of this tumor subtype and its association with five key features: mutation status of the BRAF or KRAS genes, the CpG island methylation phenotype, microsatellite instability, immune cell infiltration, and overexpression of GTPase RAC1b. Subsequently, available therapeutic approaches for targeting these molecular characteristics are presented and critically discussed.

Keywords: BRAF; Colorectal cancer; RAC1b; Serrated pathway; Therapeutic target; Tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Microsatellite Instability
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Signal Transduction
  • rac1 GTP-Binding Protein / biosynthesis
  • rac1 GTP-Binding Protein / genetics*

Substances

  • KRAS protein, human
  • RAC1 protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • rac1 GTP-Binding Protein