Cancer of the pancreas, with a 5% survival rate within five years of diagnosis, is the fourth leading cause of cancer related deaths. The main reason behind such high morbidity is poor early detection capabilities as well as inability of currently employed drugs to alleviate cancer progression. Efforts aimed at finding better drug regimens would therefore greatly benefit from a mouse model with an intrinsic marker that can indicate different stages of pancreatic tumor formation leading to cancer and reflect the effects exerted by novel drug candidates.
The research group of Associate Professor Dr. Thomas M. Wilkie at UT Southwestern Medical Center in Dallas, Texas has been characterizing the expression of a gene called Rgs16, short for Regulator of G-protein Signaling 16, in mouse pancreas for some time. His group previously showed its embryonic activation in pancreatic stem cells. Recently, teaming up with co-investigator Associate Professor Dr. Rolf A. Brekken, they looked into its possible involvement in Pancreatic Ductal Adenocarcinoma (PDA), the most common form of pancreatic cancer, in a mouse model with an early onset aggressive form of tumor development. Using a fluorescent protein to detect Rgs16 expression, the investigators found that this gene is induced by pancreatic tumor formation starting from its earliest manifestation as ductal neoplasm all the way to advanced solid tumor in a spatially and temporally coincidental manner. Exploiting the clarity and intensity of fluorescence, postdoctoral fellow Dr. Ozhan Ocal in Dr. Wilkie's group was able to represent images of pancreatic Rgs16 expression, and hence all the stages of pancreatic tumor development, quantitatively. This helped them not only lay out the progression of the disease explicitly, but also opened up a new avenue: testing drug effects on tumor growth.
Currently, chemotherapeutic intervention of pancreatic cancer is still ineffective to extend life span beyond several months. Consequently, many research groups are in hot pursuit of finding new drug targets and designing novel ones against the disease. Utilization of PDA marker Rgs16 is an exciting opportunity as it introduces a low cost and simple test environment to follow and compare the effects of different drugs with various mechanisms of action. Consequently, the use of such a marker suggests a new strategy to screen novel therapeutics in a rapid and efficient manner directly in the tumorigenic mouse.
Currently, Dr. Ocal is trying to find the best combination of available drugs that generates the largest reduction in tumor growth early on. In addition to discovering new therapeutics combinations, principal investigator Dr. Wilkie also hopes to gain insight from additional mouse models about what specific pancreatic signaling pathway Rgs16 might be acting on.
Dr. Ocal presented the findings during the Experimental Biology 2014 meeting on Monday, April 28.
The study was funded by the National Cancer Institute, the National Institute for General Medical Sciences, and a University of Texas Southwestern Cancer Center Pilot Project Award.
Materials provided by Federation of American Societies for Experimental Biology (FASEB). Note: Content may be edited for style and length.
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