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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 84-93
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.84
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.84
p53 mutations in colorectal cancer- molecular pathogenesis and pharmacological reactivation
Xiao-Lan Li, Jianbiao Zhou, Wee-Joo Chng, Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Centre for Translational Medicine, Singapore 117599, Singapore
Xiao-Lan Li, Zhi-Rong Chen, Department of Gastroenterology, Suzhou Municipal Hospital (Eastern), Suzhou 215001, Jiangsu Province, China
Wee-Joo Chng, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore
Wee-Joo Chng, Department of Hematology-Oncology, National University Hospital, Singapore 119228, Singapore
Author contributions: Li XL, Zhou J, Chen ZR and Chng WJ all reviewed the literature and wrote the manuscript; all authors approved the final version of the manuscript; and all authors contributed equally to this work and were co-first authors.
Supported by National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative; and NMRC Clinician-Scientist IRG Grant CNIG11nov38 (Zhou J); Chng WJ is also supported by NMRC Clinician Scientist Investigator award
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wee-Joo Chng, MD, PhD, Associate Professor, Department of Hematology-Oncology, National University Hospital, 1E, Kent Ridge Road, Singapore 119228, Singapore. mdccwj@nus.edu.sg
Telephone: +65-65161118 Fax: +65-68739664
Received: July 7, 2014
Peer-review started: July 8, 2014
First decision: August 6, 2014
Revised: August 20, 2014
Accepted: October 14, 2014
Article in press: October 15, 2014
Published online: January 7, 2015
Processing time: 184 Days and 0.5 Hours
Peer-review started: July 8, 2014
First decision: August 6, 2014
Revised: August 20, 2014
Accepted: October 14, 2014
Article in press: October 15, 2014
Published online: January 7, 2015
Processing time: 184 Days and 0.5 Hours
Core Tip
Core tip: Dysregulation of p53 tumor suppressor gene is one of the most frequent events contributing to the transformation of colorectal cancer (CRC), as well as the aggressive and metastatic features of CRC. Mutant p53 reactivator, PRIMA-1MET has been tested in Phase I/II clinical trials and shows encouraging benefits. In this review, we systemically and comprehensively summarize the current understanding of p53 mutations in the pathogenesis of CRC and current progress in reactivation of p53 as a novel therapeutic strategy. We hope this review will promote more investigations of reactivation of p53 as a viable treatment option of patients with CRC.