Molecular markers predictive of chemotherapy response in colorectal cancer

Curr Gastroenterol Rep. 2015 Feb;17(2):431. doi: 10.1007/s11894-015-0431-7.

Abstract

Recognition of the molecular heterogeneity of colorectal cancer (CRC) has led to the classification of CRC based on a variety of clinical and molecular characteristics. Although the clinical significance of the majority of these molecular alterations is still being ascertained, it is widely anticipated that these characteristics will improve the accuracy of our ability to determine the prognosis and therapeutic response of CRC patients. A few of these markers, such as microsatellite instability and the CpG island methylator phenotype (CIMP), show promise as predictive markers for cytotoxic chemotherapy. KRAS is a validated biomarker for epidermal growth factor receptor (EGFR)-targeted therapy, while NRAS and PI3KCA are evolving markers for targeted therapies. Multiple new actionable drug targets and potential response biomarkers are being identified on a regular basis, but most are not ready for clinical use at this time. This review focuses on key molecular features of CRCs and the application of these molecular alterations as predictive biomarkers for CRC.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • CpG Islands / genetics
  • DNA Methylation
  • ErbB Receptors / antagonists & inhibitors
  • Humans
  • Microsatellite Instability
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Phenotype
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics
  • ras Proteins / genetics

Substances

  • Angiogenesis Inhibitors
  • Biomarkers, Tumor
  • ErbB Receptors
  • Mitogen-Activated Protein Kinase Kinases
  • Phosphatidylinositol 3-Kinases
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • Tumor Suppressor Protein p53
  • ras Proteins
  • KRAS protein, human
  • BRAF protein, human