Promising early results for a new drug for pancreatic cancer have been reported by UK and US scientists this year at the Annual Meeting of the American Gastroenterological Association and just published this week in the online section of the journal Molecular Cancer Therapeutics. The new drug targets an enzyme called PKD, an enzyme discovered by Dr. Enrique Rozengurt, who presently holds the Ronald S. Hirshberg Chair for Translational Pancreatic Cancer Research at UCLA. Since its discovery in 1994 at the Cancer Research, UK in London, PKD has been shown to play a central role in a variety of fundamental cellular processes and activities, including cell proliferation, survival and formation of new blood vessels.
The growth promoting effect of PKD on human pancreatic cancer cells has been a major focus of the research in Dr Rozengurt’s laboratory at UCLA and this research has been greatly supported by the Hirshberg Foundation for Pancreatic Cancer Research. Drs Sushovan Guha and Krisztina Kisfalvi, both mentored by Dr Rozengurt, have presented recently their results on the role of PKD on this deadly cancer at several national scientific meetings (Digestive Diseases Week, Annual Meeting of the American Pancreatic Association) and another recent paper published in Journal of Cellular Physiology illustrated some of these effects. The work of Dr Rozengurt strongly raised the possibility that PKD is a therapeutic target in pancreatic cancer and other aggressive solid cancers.
As PKD became increasingly recognized as a potentially key target in tumors, an intensive drug discovery effort at the Cancer Research Technology, UK, culminated in the identification of CRT0066101, a potent orally active PKD inhibitor as a lead candidate for pre-clinical studies. Dr Guha, who is now an Assistant Professor at the MD Anderson Cancer Center at Houston, collaborated in the project and completed the research on in vivo animal models. Dr Rozengurt also participated in this research. The results show that the PKD inhibitor decreases the proliferation of pancreatic cancer cells in culture and the growth of tumors in pancreatic cancer xenograft models. Furthering the notion that PKD is a plausible target in human pancreatic cancer is the finding that its active form is greatly increased in human pancreatic cancer tissues, detected using reagents originally developed in the laboratory of Dr Rozengurt. As Dr Guha said: “We are very optimistic about CRT0066101’s pharmacological potential. We believe this is the first orally administered small-molecule inhibitor of PKD with significant biological efficacy in pre-clinical animal models of pancreatic cancer.”
These developments are funded by the Hirshberg Foundation for Pancreatic Cancer Research.