The role of the PI3K pathway in colorectal cancer

Crit Rev Oncol Hematol. 2015 Apr;94(1):18-30. doi: 10.1016/j.critrevonc.2014.12.006. Epub 2014 Dec 25.

Abstract

In the last decade treatment for colorectal cancer (CRC) has evolved with the addition of contemporary chemotherapy drugs and targeted therapies. Despite this progress, our drug armamentarium is by no means complete and modern molecular biology techniques have led to the identification of a number of 'druggable' targets. One of the most important current drug targets is the phosphatidyl-inositol 3-kinase (PI3K) pathway, which is frequently deregulated in patients with CRC. In vitro and in vivo data strongly support the clinical development of compounds affecting signal transduction via the PI3K pathway. In this review we outline the role of PI3K in the development and progression of CRC and discuss data from current and ongoing clinical trials targeting this pathway. In addition we make suggestions toward the optimization of future research in order to derive the maximum benefit for patients with CRC.

Keywords: Biomarkers; Colorectal; PI3K; PIK3CA; Predictive.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction* / drug effects

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinases