Published online Aug 7, 2014. doi: 10.3748/wjg.v20.i29.9744
Revised: March 13, 2014
Accepted: May 19, 2014
Published online: August 7, 2014
Core tip: The pro-apoptotic effects of p38α activation are long recognized; however, a significant number of reports describes the involvement of p38α in cancer-specific metabolism, survival, proliferation, and chemoresistance of colorectal cancer cells and tissues. p38α blockade exerts its chemosensitizing effects through nuclear accumulation of FoxO3A and activation of its pro-apoptotic gene expression program, thereby improving the efficacy of anti-cancer treatments. Apoptosis induction upon p38α inhibition requires Bax, which may thus serve as a predictive bio-marker for p38α-targeted therapy response. The novel role described for the p38-FoxO3A axis in chemoresistance might offer new options for combined therapies and personalized medicine approaches.