Inhibiting PAK1 increases survival of mice with pancreatic cancer
Australian researchers identify PAK1
as a regulator of the activation, proliferation, and apoptosis of pancreatic stellate cells. The study, led by researchers from the University of Melbourne and the University of New South Wales, suggests that PAK1 could be a therapeutic target for pancreatic cancer.
For many years pancreatic cancer has been looked at as a death sentence because the overall survival rates are very low. Only 6% of pancreatic cancer patients are alive five years after diagnosis. Seldom detected in its early stages, pancreatic cancer is one of the most common causes of cancer death. In the USA, about 42,500 people are diagnosed with pancreatic cancer each year, and 35,000 people die of their disease. Pancreatic cancer was the 11th most commonly diagnosed cancer in Australia in 2011, and there are 3,200 new cases of pancreatic cancer diagnosed annually with 2,900 deaths from the disease.
Mehrdad Nikfarjam, corresponding author of the current study, and colleagues set out to examine the role of p21-activated kinase 1 (PAK1) in pancreatic stellate cells (PSCs). PSCs contribute to a small proportion of all pancreatic cells but are essential for maintaining the normal pancreatic architecture. An increasing body of evidence suggests that activated PSCs play a key role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. The protein PAK1 regulates a wide variety of cellular processes such as cell motility and morphology, and it may have a role in signaling pathways involving PSCs.
The study showed that PAK1 was expressed in isolated human PSCs, and a PAK inhibitor called FRAX597 decreased the activation of PSCs, inhibited the proliferation of PSCs, and promoted apoptosis in PSCs. Using mouse models of pancreatic cancer, the researchers found that reducing PAK1 expression and activity resulted in increased survival. The study was published 7 February 2017 International Journal of Cancer.