The P13 kinase pathway

Friday, 22 January 2010 17:02

Research news

A novel therapeutic target in the treatment of IBD and colorectal cancer?

The relationships between inflammation and cancer have been the object of a number of studies, and it was demonstrated that, in comparison with the general population, patients with chronic inflammatory diseases of the intestinal mucosa (inflammatory bowel disease,   IBD) have an increased risk of developing colorectal cancer.  Nevertheless, the molecular mechanisms behind cancer development in these patients remain  poorly understood.  In an article published in Gastroenterology, Ana Gonzalez-Garcia and colleagues demonstrate the role of the gamma isoform  of PI kinase (PI3Kg) in an animal (mouse) model of IBD and colorectal cancer¹.

In this study, mice deficient in PI3Kg  showed the following:

•  Reduced gut inflammation as well as a decrease in the incidence and number of tumors, correlated with a decrease in neutrophil, macrophage and CD4+  recruitment and a reduction in synthesis of inflammatory cytokines (IL-1b, IL-6 and TNF-a).
•  An increased concentration of gdT cells, known to exert a protective effect during the course of inflammation.

These results underline the important role of the PI3K pathway in regulation of the immune response.  Consequently, specific inhibitors of the PI3K pathway, and in particular, PI3Kg, could constitute a new therapeutic approach in the treatment of IBD and associated cancers.

Reference

Gonzalez-Garcia, A., Sanchez-Ruiz, J., Flores, J. M. & Carrera, A. C. Phosphatidylinositol 3-kinase gamma inhibition ameliorates inflammation and tumor growth in a model of colitis-associated cancer. Gastroenterology (2009).