Targeting PI3K signaling as a therapeutic approach for colorectal cancer

Gastroenterology. 2011 Jul;141(1):50-61. doi: 10.1053/j.gastro.2011.05.010.

Abstract

Survival times of patients with colorectal cancer (CRC) have increased over the past decade, primarily as a result of treatment with combinations of conventional cytotoxic agents. Because CRC is commonly associated with mutations in genes that control growth factor signaling, therapies are being developed to target the products of these genes; individualized treatment might also be guided by specific mutations in tumors and by new biomarkers. Currently, targeted therapies confer limited clinical benefit; better drugs are therefore needed. Genomic studies indicate that phosphoinositide 3-kinase (PI3K) signaling is one of the most frequently deregulated pathways in several human cancers, including CRC. PI3K signaling has an important role in cancer cell proliferation, survival, motility, and metabolism and therefore could be an attractive therapeutic target. We review PI3K signaling in CRC and discuss current therapeutic approaches.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects*

Substances

  • Angiogenesis Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors