Fibrolamellar received minimal research attention prior to the founding of FCF. Since 2010 FCF has invested nearly $5 million in research, with the goal to accelerate the road to curative therapies. Research has been both in traditional and non-traditional approaches, led by respected M.D.’s and PhD’s who focus on clinical trials, translational, and basic research.
Stanford University, Palo Alto, CA
Developing pre-clinical models for fibrolamellar FL-HCC:Therapeutic target identification and testing
Principal Investigator: Dr. Julien Sage, Ph.D., Associate Professor, Department of Pediatrics and Genetics
Focus: Development of accurate pre-clinical models of fibrolamellar hepatocellular carcinoma (FL-HCC) to be used both to investigate the basic mechanisms of FL-HCC development which may help identify new therapeutic targets, and to test novel therapeutic strategies. (Read more…)
Mayo Clinic, Rochester, MN
Kinase fusion function investigation
Principal Investigator: Dr. Yi Guo, Ph.D, Associate Consultant – Asst Professor, Dept of Biochemistry and Molecular Biology
Focus: Investigating the function of the novel kinase fusion of DNAJB1-PRKACA (found in over 80% of FL-HCC patients) using both drosophila (fruit fly) and mice models. This to include screening of potent therapeutics to validate the hypothesis that decreasing the fusion kinase dosage or activity could regress the tumor progression… (Read more)
UNC School of Medicine, Chapel Hill, NC
RNA validation and evaluation of FLC, including therapeutic targets
Principal Investigator: Dr. Praveen Sethupathy, Ph.D. Assistant Professor of Genetics
Focus: Three areas (1)Validating UNC’s RNA signature of FLC in an independent set of FLC, HCC, and CCA samples (collaboration with Dr. Michael Torbenson); (2) Evaluating the expression and function of these RNAs in the first-ever transplantable FLC tumor line,TU-2010(collaboration with Dr. Lola Reid); (3) Identifying candidate therapeutic targets of FLC for future clinical development… (Read more)
Johns Hopkins University, Baltimore, MD
BLT: Sequential Partial Liver Transplant with Bone Marrow Transplantation
Principal Investigator: Dr. Ephraim Fuchs, MD, MBA, Professor of Oncology and Immunology
Focus: Purpose is to reduce the risk of cancer recurrence in patients whose cancer remains confined to the liver, but is too widespread to be surgically removed or treated by a liver transplant… (Read more)
University of North Carolina, Chapel Hill, NC
2010 to present
Principal Investigator: Lola Reid, PhD, Professor, University of North Carolina, Chapel Hill
Dr.Reid is working with FCF Founder Tucker Davis’ cancer cells to determine where these cells start within the stem cells of the biliary tree. Dr. Reid has found a way to culture Tucker’s cells and grow them to provide more cells for other labs’ research. She is presently giving Tucker’s cancer cells to immunosuppresed mice with the hope that a specific treatment option will result from her work. Dr. Reid has shared Tucker’s cells with the National Institute of Health and Dr. Malcolm Moore at MSKCC.
The following initiatives were funded since 2010 and are listed in reverse order of funding. Research is no longer continuing on these grants.
Yale School of Medicine, New Haven, CT
Iodine Transporter Research: FCF funded Dr. Nancy Carrasco at Yale School of Medicine to analyze FLC cells to discover whether they could be effectively targeted by radioactive iodine. Radioactive iodine has a long history as a safe and effective treatment for thyroid cancer. Research had indicated that fibrolamellar cells might have pathways similar to those of thyroid cancer cells. Use of radioactive iodine on several patients did not confirm this theory and the project was terminated.
Johns Hopkins University, Baltimore, MD
Dr. Michael Torbenson while at Johns Hopkins (he is now at Mayo Clinic in Rochester, MN) wrote the first paper on blood markers for fibrolamellar which was published in the journal, Modern Pathology, in late 2010. The article recognized FCF for their financial support. While at Johns Hopkins Dr. Torbenson was studying the microRNA of fibrolamellar cells and his laboratory was working on a genetic sequencing study of fibrolamellar to determine if there are genetic mutations unique to fibrolamellar cells.
Rockefeller University, New York, NY
FCF funding to Rockefeller University resulted in a potentially game-changing discovery of a unique genetic mutation common to all fibrolamellar tissues studied, a chimera. This research was conducted at the Tucker Davis Research Facility at Rockefeller University. Dr. Sandy Simon is head of that facility and his daughter Elana, who is a fibrolamellar patient, was a lead researcher. The results were published in the preeminent medical journal, Science and reported in The Wall Street Journal, US News and World Report, AP, The Today Show, NBC Nightly News, and presented to President Obama.
The Foundation granted Dr. Sandy Simon funds to study immunotherapy and fibrolamellar. Rockefeller University has put their full support behind Dr. Simon and charges no administrative fees for this research. Rockefeller University has provided Dr. Simon with a dedicated space exclusively for fibrolamellar research, The Tucker Davis Fibrolamellar Research Facility. FCF provided a freezer for fibrolamellar tissue samples. Dr. Simon’s goal is finding a cure – total eradication from the body. He feels this path is through the immune system using the patients’ own antibodies to track and kill the cancer cells. His research also includes melanoma and breast cancer cells.
Dr. Simon has already discovered a way to extract antibodies from a patient, mark them, and re-introduce them into the body. The marked antibodies can attach to the smallest of cancer cells which will help surgeons and pathologists determine, during surgery, whether all the cancer has been removed.
Memorial Sloan Kettering Cancer Center, New York, NY
FCF funded the first clinical trial of drugs aimed specifically at fibrolamellar liver cancer. This trial was coordinated by Dr. Ghassan Abou-Alfa at Memorial Sloan Kettering Cancer Center (MSKCC). The trial was also at other consortium members, the University of California San Francisco, Johns Hopkins, and Dana Farber. Two major pharmaceutical companies are donating the drugs. While the trial is ongoing for exisiting patients no new patients are being accepted.
MSKCC is sequencing the exome of the fibrolamellar genome.
MSKCC is the coordinator of the Fibrolamellar Consortium.
British Columbia Cancer Center, Canada
Dr. Y.Z. Wang published his findings on the microRNA research he is doing on cancer. He has thanked FCF for supporting his effort. His findings will help other microRNA researchers who are studying other cancers, ie. Dr. Torbenson at Johns Hopkins University who is studying microRNA of fibrolamellar. Dr. Wang’s paper sets an important precedent in cancer research in that it reports discrete molecular (microRNA) differences between tumors which metastasize and perfectly matched tumors that do not. These findings may have diagnostic, prognostic and most important of all, therapeutic implications.
FCF has funded the creation of The Fibrolamellar Consortium in 2011. This is a collaborative effort by Memorial Sloan- Kettering (NYC), Johns Hopkins (Baltimore), University of California/San Francisco, University of Texas Southwestern Medical Center, Dallas, Texas, and Dana Farber (Boston). The consortium’s mission is to:
- promote awareness about FLC within the oncology community
- develop new therapies for FLC
- pool information on FLC patients in order to document trends in diagnosis, treatment and survival.
The consortium conducted a clinical trial, now closed, which tested a novel treatment designed specifically for FLC. This was the first clinical trial dedicated to patients with advanced FLC that cannot be treated with surgery.
The Consortium meets twice a year at the ASCO (American Society of Clinical Oncology) converntions. The Consortium had a poster presentation at the ASCO convention in Chicago, June 2011. This generated a lot of interest and queries about fibrolamellar research.
FIBROLAMELLAR SCIENTIFIC CONFERENCE
In an effort to bring the best medical and scientific minds together who are involved in studying and treating fibrolamellar, the Foundation hosted a the first ever scientific conference to focus exclusively on this disease in April 2014. There were over 40 people in attendance, including fibrolamellar researchers and clinicians who treat fibrolamellar patients including representatives from major cancer centers in the U.S., Canada and Israel including Memorial Sloan-Kettering, Dana Farber, Johns Hopkins, Mayo Clinic, MD Anderson, Seattle Cancer Center, UCSF, British Columbia Cancer Center, Vanderbilt Ingram and the International Center for Cell Therapy and Cancer Immunology. There were scientists from Yale, Rockefeller, Columbia, Johns Hopkins, University of North Carolina and the NIH. The retired pathologist who gave this cancer its name, FCF Board member Dr. John Craig, was also present.
Over the course of the day there were multiple presentations with opportunities for questions. Recent significant findings were reported by several of the scientists some of which could be the foundation for future treatments. There were fascinating discussions about psychiatric symptoms and other previously unrecognized commonalities amongst some fibrolamellar patients. While much of the research is preliminary it presents interesting and hopeful avenues to pursue.