Grossi V, Peserico A, Tezil T, Simone C. p38α MAPK pathway: A key factor in colorectal cancer therapy and chemoresistance. World J Gastroenterol 2014; 20(29): 9744-9758 [PMID: 25110412 DOI: 10.3748/wjg.v20.i29.9744]
Corresponding Author of This Article
Cristiano Simone, MD, PhD, Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro”, Via Nazionale 8/A, Bari 70124, Italy. simone@negrisud.it
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Topic Highlight
Open-Access Policy of This Article
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Valentina Grossi, Alessia Peserico, Tugsan Tezil, Cristiano Simone, Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro”, 70124 Bari, Italy
Valentina Grossi, Alessia Peserico, Tugsan Tezil, Cristiano Simone, National Cancer Institute, IRCCS Oncologico Giovanni Paolo II, 70124 Bari, Italy
Alessia Peserico, Fondazione Mario Negri Sud, Santa Maria Imbaro 66030 (CH), Italy
Author contributions: All authors contributed to the manuscript.
Supported by Italian Association for Cancer Research (AIRC) fellowship (to Grossi V); Italian Foundation for Cancer Research (FIRC) fellowships (to Peserico A and Tezil T); Investigator Grant 2010 No. IG10177 to Simone C from the Italian Association for Cancer Research (AIRC) and by FIRB “Futuro in Ricerca” RBFR12VP3Q_003 (to Simone C) from the Italian MIUR
Correspondence to: Cristiano Simone, MD, PhD, Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari “Aldo Moro”, Via Nazionale 8/A, Bari 70124, Italy. simone@negrisud.it
Telephone: +39-87-2570210 Fax: +39-87-2570299
Received: November 5, 2013 Revised: March 13, 2014 Accepted: May 19, 2014 Published online: August 7, 2014
Core Tip
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.
