Division of Surgical Oncology Associate Professor Sean Ronnekleiv-Kelly, MD, is determined to improve treatment options for a rare but deadly form of liver cancer called fibrolamellar carcinoma (FLC). With a new two-year, $276,000 grant from the Fibrolamellar Cancer Foundation, he is aspiring to doing so.
Typically affecting adolescents and young adults, FLC tends to occur in people who have healthy livers. It is often diagnosed at an advanced stage, which makes FLC much harder to treat and results in poor patient outcomes: only 30-45% of people with FLC are still alive 5 years after their diagnosis. Better treatment strategies are critically needed, and for the last few years the Ronnekleiv-Kelly lab has been studying FLC in animal models and in human tissue. This led to the discovery of a protein that wasn’t functioning properly in patients with FLC.
“We found that this protein, CDK7, is unexpectedly activated in FLC cancer cells, and that its presence alters gene expression in a way that can cause the cancer cells to multiply more quickly,” explained Ronnekleiv-Kelly. “We also found that manipulating CDK7 to inhibit its function can actually cause FLC cancer cells to die. This tells us that CDK7 inhibition could potentially be a good target for drug development.”
With his new grant from the Fibrolamellar Cancer Foundation, Ronnekleiv-Kelly will be testing this theory by transplanting human FLC tumor tissue into mice, which is the next step to help the researchers determine if targeting CDK7 could be a way to treat FLC. This will allow them to look more closely at how CDK7 inhibition works and whether it has any side effects. They will also be able to combine it with other promising drugs to see if the combination of drugs is more powerful than one drug alone in killing FLC cancer cells.
“The peak age of diagnosis for FLC is 22 years, so this disease has an enormous impact on life-years lost. If our investigations into CDK7 are successful, this could be helpful in terms of advancing treatments for this rare and lethal disease,” said Ronnekleiv-Kelly.
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.