Just before he turned 27, Tucker Davis was diagnosed with fibrolamellar hepatocellular carcinoma (FL-HCC). FL-HCC is a rare liver cancer that usually occurs in adolescents and young adults who have no history of liver disease. FL-HCC has an incidence rate of 1 in 5,000,000 in the population at large. Ultra-rare cancers are defined as those with fewer than 1000 cases per year; FL-HCC is diagnosed in approximately 200-300 patients each year in the United States.
Shortly after being diagnosed, Tucker, along with three friends, Alisha Sternenberger, Charles Beermann, and Derek Gilchrist, founded the Fibrolamellar Cancer Foundation (FCF). The mission of FCF is to find a cure and treatment options for FL-HCC, raise awareness for the disease, and connect and support the community of FL-HCC patients and families. Since FCF was founded in 2009, they have invested approximately $6 million dollars in research.
To help find a cure and new treatment options for FL-HCC, FCF funds research at world class institutions, including Stanford University School of Medicine. Julien Sage, PhD, professor of pediatric Hematology/Oncology and Genetics, received a $292,242, two-year grant from FCF to develop a pre-clinical mouse model of FL-HCC. Clinical trials for FL-HCC are limited by the fact that it is such a rare disease, occurring mostly in adolescents and young adults. Developing accurate pre-clinical models is imperative to develop better therapies for patients with FL-HCC. These models can be used to investigate the basic mechanisms of FL-HCC development, potentially identifying new therapeutic targets, and to test novel therapeutic strategies. Though FL-HCC is an ultra-rare cancer, the hope of Dr. Sage and FCF is that some of what is learned from FL-HCC research can be applied to other types of cancer. As Dr. Sage explains, “My initial interest in FL-HCC came from my past work in rare pediatric cancers such as retinoblastoma. Many of these rare tumors can teach us a lot about fundamental mechanisms of tumorigenesis.”
After the first year of the grant, FCF’s Executive Director John Hopper and Board of Directors member John Craig, MD, PhD, visited Dr. Sage and his lab to learn more about the progress of the project. Dr. Craig, a pathologist who was responsible for naming FL-HCC, also leads FCF’s Grant Review Committee. Pam Craig, MD, PhD, Dr. John Craig’s wife, also attended the meeting with Dr. Sage. The FCF contingent took a tour of Dr. Sage’s lab and then listened to a presentation from Garry Coles, PhD, a postdoctoral scholar in Dr. Sage’s lab. Dr. Coles shared results of the team’s efforts to develop strains of mice containing a distinct genetic alteration that results in the fusion of two proteins, DnaJB1 and PKA. This fusion has been found to be present in all FL-HCC tumors sequenced so far, including patients sequenced at Stanford as a collaboration between Dr. Sage’s team, Dr. Arun Rangaswami (clinical oncologist at Lucile Packard Children’s Hospital Stanford), Dr. Florette Hazard (pathologist at Stanford University Medical Center), and Dr. Michael Snyder (director of the Center for Genomics and Personalized Medicine at Stanford University). If the fusion protein causes tumors in the mice strains that Dr. Sage and Dr. Coles are developing, it will conclusively demonstrate that its expression is an essential step in FL-HCC tumor growth and provide novel insights into FL-HCC development. The generation of mice that develop FL-HCC tumors that resemble human tumors would provide a valuable pre-clinical platform to test new therapies. “The investigative work of Dr. Sage’s impressive team is critical to accelerating the road to curative therapies for fibrolamellar patients,” notes FCF’s John Hopper. “As an important part of the FCF community, Stanford’s unique approach will play a critical role near and long term in both basic and translational research.”
Stanford School of Medicine research is on the leading edge because of its faculty’s collaborative, interdisciplinary approach to solving the world’s most complex problems. “Stanford is a unique place to study diseases such as FL-HCC, with an outstanding group of physicians involved in treating children with liver cancer and unique technologies to investigate the biology of liver cancer cells, including advanced genetics, genomics, and proteomics approaches,” explained Dr. Sage. “I have always been interested in pediatric and developmental diseases, and I believe that Stanford University is an incredible and collaborative scientific community that is an ideal setting for asking questions about the origin of diseases such as FL-HCC,” echoes Dr. Coles.
In addition to being happy to study under an accomplished mentor in Dr. Sage, Dr. Coles is also optimistic about their FL-HCC research: “I am excited to perform my postdoctoral training at Stanford University under the guidance of Dr. Sage. I believe that our work will enhance our understanding of the biology of FL-HCC and provide information to aid in the design of future therapies.”
