PHILADELPHIA Molecular biologist Jonathan Brody, Ph.D., assistant professor, Department of Surgery; and Gregory E. Goney, Ph.D., research assistant professor, and member of the Daniel Baugh Institute for Functional Genomics/Computational Biology in the Department of Pathology, Anatomy and Cell Biology at Jefferson Medical College of Thomas Jefferson University have been awarded a W.W. Smith Charitable Trust medical research grant. This one-year grant awards $100,000 to their group to help support their innovative cancer research, and one of the questions they will address is why African-Americans respond poorly to common chemotherapeutic agents used to treat pancreatic cancer. Another question this grant will address is what genes in cancer cells are regulated upon stressful conditions such as chemotherapeutic treatments..
Dr. Brody will use the funding to build upon his research involving a stress-response protein called Hu antigen R (HuR), which helps pancreatic tumor cells survive. Previously, Dr. Brody and his team have identified the molecular mechanism by which HuR regulates gemcitabine (a commonly used drug used to treat this disease). Recently, the team has discovered a unique DNA sequence alteration that resides in the HuR-interacting site of deoxycytidine kinase, the gemcitabine activating enzyme. This one base pair sequence change, also known as a polymorphism (SNP), is highly prevalent in the African-American population (over 65 percent); it is considerably less common in the Caucasian population (5 percent). From preliminary data, this sequence change may explain why African Americans respond poorly to standard of care therapy of pancreatic cancer.
"Our early findings are very exciting. It's our hope that further validation and exploration of this particular polymorphism may ultimately result in a simple test that could improve therapy and outcomes for African Americans with this deadly disease," said Dr. Brody.
A unique aspect of this work is the interdisciplinary team built by Dr. Gonye and Dr. Brody. Using genome-scale technologies in combination with computational analyses the team will identify not only specific molecular changes but the biological context those changes affect. "By applying systems biology approaches to HuR biology in the context of pancreatic cancer we will greatly improve our chances of identifying truly novel opportunities for intervention in this terrible disease." said Dr. Gonye. "I'd like to thank W.W. Smith Charitable Trust for supporting this 'out of the box' project in regards to pancreatic cancer and for seeing the potential clinical value in this research." added Dr. Brody.
Dr. Brody's research will hopefully lead to a better understanding and more targeted treatment therapies for pancreatic cancer. His team's research will address subtle genetic sequence alterations that are found commonly in ethnic patient populations; and will further explore HuR, a potent regulator of gene expression levels in pancreatic cancer cells. These are two very important aspects of cancer biology that are often underappreciated. Further exploring the recently discovered interaction between HuR and the enzyme responsible for common chemotherapeutic efficacy will aid in our goal to explore a genetic basis for why African-American cancer patients do not respond well to a cancer therapy. At the same time, new core signaling pathways or altered gene regulation may be discovered that disrupt cancer in cells. "We believe this work is unique and will eventually have a major impact on pancreatic cancer research and eventually the treatment of this devastating disease. We need to patiently do these careful basic studies first before moving into our patient samples and translating this work to the clinic." said Dr. Brody.
This research will hopefully provide seminal work for understanding ethnic disparities that exist in the treatment of cancer and will, at the same time, provide novel insights into how a normal cell becomes cancerous.