Division of Surgical Oncology Associate Professor Sean Ronnekleiv-Kelly, MD, has devoted much of his scientific career to the study of fibrolamellar cancer, a rare but deadly form of liver cancer that affects young adults. So when researchers discovered that a gene mutation caused by two specific genes fusing together may be a driver of not only fibrolamellar cancer but also equally rare and lethal cancers of the pancreas and bile duct, he saw an opportunity to scientifically attack three cancers with one proverbial stone: a new two-year, $528,000 grant from the Fibrolamellar Cancer Foundation.
“The gene that has been linked to all three cancers is the DNAJB1-PRKACA mutation,” said Ronnekleiv-Kelly. “It’s a mutation that my lab has been studying for the last six years, and it’s one for which we developed a mouse model that allows us to introduce the mutation into specific cells of mouse organ systems, including the liver, pancreas, and bile ducts, so we can monitor these mutant cells to see how they change over time.”
Working with a pathologist at the Mayo Clinic in Rochester, Ronnekleiv-Kelly will use this mouse model and tap into the resources of the cutting-edge UW Biotechnology Center to confirm the biological overlap of DNAJB1-PRKACA as a cause for all three forms of cancer. The research team will also examine another gene, SLC16A14, the over-expression of which was discovered by researchers at Cornell University and has been strongly linked to fibrolamellar cancer. If SLC16A14 is similarly over-expressed in other biliary and pancreatic cancers, it could present a potential target for the development of new therapies.
“Because these cancers are not common, progress in our ability to diagnose and effectively treat them has been slow to date,” explained Ronnekleiv-Kelly. “With the support of the Fibrolamellar Cancer Foundation, our research will provide the unique opportunity to unravel how DNAJB1-PRKACA causes cancer formation and the relevance of SLC16A14 in DNAJB1-PRKACA driven cancers; this should lead to significant advancements for three separate rare and lethal cancers.”
About the Fibrolamellar Cancer Foundation:
The principal purpose of the Fibrolamellar Cancer Foundation (FCF) is to encourage, drive and fund research that will substantially improve outcomes for patients with fibrolamellar carcinoma (FLC), a rare form of liver cancer that primarily occurs in adolescents and young adults who have no history of liver disease. FCF, a public 501(c)(3) nonprofit organization based in Greenwich, CT, was founded in 2009 by Tucker Davis, a FLC patient. Today, FCF is the leading non-governmental funder of FLC research. By supporting cutting-edge research, actively recruiting investigators, and working collaboratively to understand the disease’s origins, FCF hopes to develop more effective therapies and ultimately a cure for FLC. 100% of all donations directly fund FLC research.