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The Role of p21-Activated Kinases in Pancreatic Cancer

Yeo, Dannel B.Biomed(Hons); He, Hong MD, PhD; Baldwin, Graham S. PhD, DSc; Nikfarjam, Mehrdad MD, PhD, FRACS

doi: 10.1097/MPA.0000000000000276

Pancreatic cancer is an aggressive cancer with a poor prognosis and an overall 5-year survival rate of less than 5%. Management has not improved significantly over the last 30 years, and a better understanding of the genetic and molecular changes that occur is urgently required. Many of these changes appear to involve the p21-activated kinases (PAKs). The PAK family consists of 6 isoforms, 2 of which, PAK1 and PAK4, are up-regulated and/or hyperactivated in pancreatic cancer. p21-Activated kinases can mediate many different cellular processes especially those contributing to cancer development and progression. These processes include the regulation of cytoskeletal dynamics and cell adhesion, the evasion of apoptosis, and the promotion of cell survival, proliferation, migration, and invasion. p21-Activated kinases may also be involved in characteristics unique to pancreatic tumors, such as interplay with the pancreatic stroma, the re-emergence of embryonic pathways, and the involvement of a subset of microRNAs and heat shock proteins. This review highlights the potential role of PAKs in pancreatic cancer and provides a foundation for more effective therapeutics to improve our current treatment of pancreatic cancer.

From the Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia.

Received for publication April 7, 2014; accepted August 22, 2014.

Reprints: Mehrdad Nikfarjam, MD, PhD, FRACS, University Department of Surgery, Austin Health, Studley Rd, Heidelberg, Melbourne, Victoria 3084, Australia (e-mail:

D.Y. is supported by Australian Rotary Health (The Ian Loxton Pancreatic Cancer Research PhD Scholarship).

The authors declare no conflict of interest.

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