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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2016; 22(3): 1224-1235
Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.1224
Group II p21-activated kinases as therapeutic targets in gastrointestinal cancer
Yang-Guang Shao, Ke Ning, Feng Li
Yang-Guang Shao, Ke Ning, Feng Li, Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, Liaoning Province, China
Author contributions: Shao YG wrote and organized the manuscript; Ning K searched reference materials and contributed to the writing of the manuscript; Li F designed the study, outlined the draft, and supervised the overall project.
Supported by National Natural Science Foundation of China, No. 90813038, No. 31271389, No. 31371424, No. 31171360 and No. 81230077.
Conflict-of-interest statement: The authors have no conflict of interest to report.
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: Feng Li, PhD, Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, No. 77 Puhe Road, Shenbei District, Shenyang 110122, Liaoning Province, China. fli@mail.cmu.edu.cn
Telephone: +86-24-23261056 Fax: +86-24-23261056
Received: May 8, 2015
Peer-review started: May 11, 2015
First decision: August 31, 2015
Revised: September 17, 2015
Accepted: November 19, 2015
Article in press: November 19, 2015
Published online: January 21, 2016
Abstract

P21-activated kinases (PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group I (PAK1-3) and group II (PAK4-6). Focus is currently shifting from group I PAKs to group II PAKs. Group II PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group II PAKs have become popular potential drug target candidates. However, few group II PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and “drug-like” properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group II PAKs, the importance of group II PAKs in the development and progression of gastrointestinal cancer, and small-molecule inhibitors of group II PAKs for the treatment of cancer.

Keywords: Group II p21-activated kinases, Signaling pathway, Gastrointestinal cancer, PAK4 inhibitor, Drug target

Core tip: Group II p21-activated kinases (PAKs) (PAK4, 5 and 6) are pluripotent kinases that regulate many fundamental cellular processes, including cytoskeletal organization, cell cycle regulation, cell survival and cell adhesion, and have therefore been implicated in carcinogenesis and cancer progression. Members of the group II PAKs, particularly PAK4, have emerged as attractive targets for the development of anticancer drugs. In this review, we summarize the latest findings on the biological activities of group II PAKs, the important roles of group II PAKs in gastrointestinal cancer and the current status of the development of small-molecule inhibitors of PAK4 for the treatment of cancer.