p21-activated kinase signalling in pancreatic cancer: New insights into tumour biology and immune modulation

doi:10.3748/wjg.v24.i33.3709

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Sep 7, 2018; 24(33): 3709-3723
Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3709

p21-activated kinase signalling in pancreatic cancer: New insights into tumour biology and immune modulation

Kai Wang, Graham S Baldwin, Mehrdad Nikfarjam, Hong He

Kai Wang, Graham S Baldwin, Mehrdad Nikfarjam, Hong He, Department of Surgery, University of Melbourne, Melbourne 3084, Australia

Author contributions: Wang K reviewed the literature and drafted the manuscript; He H, Baldwin GS and Nikfarjam M revised the manuscript; all authors approved the final version of this review.

Conflict-of-interest statement: No potential conflicts of interest.

Correspondence to: Hong He, MD, PhD, Senior Research Fellow, Department of Surgery, University of Melbourne, Austin Health, 145 Studley Rd., Heidelberg 3084, Victoria, Australia. hong.he@unimelb.edu.au

Telephone: +61-3-94965468

Received: May 22, 2018
Peer-review started: May 23, 2018
First decision: June 11, 2018
Revised: June 22, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: September 7, 2018
Processing time: 106 Days and 20 Hours

Core Tip

Core tip: Pancreatic cancer is still one of the most lethal malignancies, with a five-year survival of less than 8%. The dismal prognosis is largely the result of reprogramming of the tumour microenvironment, which leads to chemo-resistance and high aggressiveness. So far, combination chemotherapies can only marginally improve patients’ survival, but with high toxicity. Therefore, alternative treatment targeting protein kinase signalling has been proposed. As downstream effectors of Kras signalling, p21-activated kinases (PAKs) are positioned at the nexus of multiple oncogenic signalling pathways. Here, the importance of PAKs as therapeutic targets in Kras signalling is discussed, and their essential role in tumour biology and immune modulation within the tumour microenvironment is highlighted.