Journal article
A framework for fibrolamellar carcinoma research and clinical trials
Nature reviews. Gastroenterology & hepatology, Vol.19(5), pp.328-342
05/01/2022
DOI: 10.1038/s41575-022-00580-3
PMCID: PMC9516439
PMID: 35190728
Abstract
In this Roadmap, Furth, Sethupathy and colleagues discuss advances in our understanding of the mechanisms and treatments of fibrolamellar carcinoma, a rare hepatic cancer that primarily occurs in adolescents and young adults. Recommendations for future progress in research and clinical trials are proposed.
Fibrolamellar carcinoma (FLC), a rare, lethal hepatic cancer, occurs primarily in adolescents and young adults. Unlike hepatocellular carcinoma, FLC has no known association with viral, metabolic or chemical agents that cause cirrhosis. Currently, surgical resection is the only treatment demonstrated to achieve cure, and no standard of care exists for systemic therapy. Progress in FLC research illuminates a transition from an obscure cancer to one for which an interactive community seems poised to uncover fundamental mechanisms and initiate translation towards novel therapies. In this Roadmap, we review advances since the seminal discovery in 2014 that nearly all FLC tumours express a signature oncogene (DNAJB1-PRKACA) encoding a fusion protein (DNAJ-PKAc) in which the J-domain of a heat shock protein 40 (HSP40) co-chaperone replaces an amino-terminal segment of the catalytic subunit of the cyclic AMP-dependent protein kinase (PKA). Important gains include increased understanding of oncogenic pathways driven by DNAJ-PKAc; identification of potential therapeutic targets; development of research models; elucidation of immune mechanisms with potential for the development of immunotherapies; and completion of the first multicentre clinical trials of targeted therapy for FLC. In each of these key areas we propose a Roadmap for future progress.
Details
- Title: Subtitle
- A framework for fibrolamellar carcinoma research and clinical trials
- Creators
- Timothy A. Dinh - University of North Carolina at Chapel HillAlan F. Utria - University of WashingtonKevin C. Barry - Fred Hutch Cancer CenterRosanna Ma - Cornell UniversityGhassan K. Abou-Alfa - Memorial Sloan Kettering Cancer CenterJohn D. Gordan - UCSF Helen Diller Family Comprehensive Cancer CenterElizabeth M. Jaffee - Sidney Kimmel Comprehensive Cancer CenterJohn D. Scott - University of WashingtonJessica Zucman-Rossi - InsermAllison F. O'Neill - Harvard UniversityMark E. Furth - Fibrolamellar Cancer FoundationPraveen Sethupathy - Cornell University
- Resource Type
- Journal article
- Publication Details
- Nature reviews. Gastroenterology & hepatology, Vol.19(5), pp.328-342
- DOI
- 10.1038/s41575-022-00580-3
- PMID
- 35190728
- PMCID
- PMC9516439
- NLM abbreviation
- Nat Rev Gastroenterol Hepatol
- ISSN
- 1759-5045
- eISSN
- 1759-5053
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 15
- Grant note
- R01DK119186 / National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P50CA062924 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 05/01/2022
- Academic Unit
- Surgery
- Record Identifier
- 9985014847802771
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