Obesity, the PI3K/Akt signal pathway and colon cancer

Obes Rev. 2009 Nov;10(6):610-6. doi: 10.1111/j.1467-789X.2009.00607.x. Epub 2009 Jun 12.


Obesity is currently reaching epidemic levels worldwide and is a major predisposing factor for a variety of life-threatening diseases including diabetes, hypertension and cardiovascular diseases. Recently, it has also been suggested to be linked with cancer. Epidemiological studies have shown that obesity increases the risk of colon cancer by 1.5-2 fold with obesity-associated colon cancer accounting for 14-35% of total incidence. Several factors, altered in obesity, may be important in cancer development including increased levels of blood insulin, insulin-like growth factor I, leptin, TNF-alpha, IL-6 as well as decreased adiponectin. A unifying characteristic of all these factors is that they increase the activity of the PI3K/Akt signal pathway. The PI3K/Akt signal pathway in turn activates signals for cell survival, cell growth and cell cycle leading to carcinogenesis. Here we review the evidence that PI3K/Akt and its downstream targets are important in obesity-associated colon cancer and thus, that targeted inhibition of this pathway could be employed for the prevention of obesity-associated colon cancer and incorporated into the therapy regime for those with irremovable colon cancers.

Publication types

  • Review

MeSH terms

  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / epidemiology*
  • Colonic Neoplasms / prevention & control
  • Comorbidity
  • Enzyme Inhibitors
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Interleukin-6 / metabolism
  • Leptin / metabolism
  • Obesity / enzymology
  • Obesity / epidemiology*
  • Obesity / prevention & control
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / physiology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Enzyme Inhibitors
  • Interleukin-6
  • Leptin
  • Tumor Necrosis Factor-alpha
  • Insulin-Like Growth Factor I
  • Proto-Oncogene Proteins c-akt