Fibrolamellar cancer (FLC) is a rare tumor of adolescents and young adults occurring in 1 in 5 million that arises as a large mass in the liver and tends to metastasize early.
The management of FLC is surgical but up to 30% of patients cannot undergo surgery and must rely upon systemic therapies. Unfortunately, the tumor is not highly responsive to most chemotherapies and new approaches are desperately needed.
Three years ago, I was contacted by Thomas Stockwell whose son Robert was diagnosed with FLC at the age of 18 and died from complications of his disease 3 ½ years later. Tom began FibroFighters to support research and development in this difficult cancer. When Tom asked if we could apply our laboratory platform to study this disease we were only too pleased to begin the collaboration.
The Fibrolamellar Cancer Foundation (FCF) is an organization based in Connecticut that is dedicated to the study and treatment of FLC. The FCF principals kindly invited me to participate in a symposium on FLC held on September 29, 2022. The meeting was chaired by Mark Furth, PhD scientific director, and Kurt Losert, CEO. Among the participants was Praveen Sethupathy from Cornell University and Eytan Ruppin, MD, PhD from the National Cancer Institute.
The discussion explored the application of multiple platforms (multi-omics) for the study of this rare condition, including genomic (DNA), transcriptomic (RNA), and proteomic (protein). Dr. Sethupathy described the use of transcriptomics (RNA) to probe gene expression while Dr. Ruppin described highly sophisticated bio-informatic platforms to examine operative pathways, including new approaches to identify candidates for immunotherapy
I described our use of fresh tumor biopsy explants to interrogate drug effects in FLC patients and explained that cellular response to drugs offers a system-biology lens as a conduit from scientific breakthrough to clinical application.
As it can sometimes be decades before research advances become clinical realities, FLC patients often do not have time to wait and we’d like to apply our platform to bring the bench discoveries to the bedside. Describing this as a “bottom-up” approach we find answers and then pursue the operative questions.
To date, we have conducted 28 analyses on FLC patients with several interesting findings including metabolic signatures and activity for Vitamin A derivatives.
The FCF meeting was very productive and attended by many patients and their family members. It is my hope that our “bottom-up” hands-on approach working with “top-down” scientists will meet in the middle, providing new, effective therapies for FLC.