Timeframe: 2017 – 2019
Goal: Understand growth mechanisms and identify potential therapeutic targets
Principal Investigator: Raymond Yeung, MD, Professor of Surgery
Fibrolamellar cancer (FLC) is the most lethal form of liver cancer in adolescents and young adults. Currently, there is no effective therapy for these patients besides surgery. With the identification of a unique genetic defect that affects nearly all FLCs (the DNAJB1-PRKACA gene fusion), the opportunity to find a cure for this disease is now within reach. Armed with a novel set of immortalized cell lines developed at the University of Washington that bear the FLC mutation, this study aimed to advance our understanding of the mechanisms that drive FLC development by:
- Identifying protein kinase pathways that are activated downstream of the mutation using a combination of global and targeted phosphoproteomic analyses.
- Functionally validating these results using FLC cell lines as well as human FLC samples.
- Investigating the role of HSPs in FLC, including their pro-survival function in keeping cells alive during stress, based on preliminary observations that the mutant protein associates with heat shock protein (HSP) 70.
Together, these studies aimed to unveil mechanistic insights and new therapeutic targets that will accelerate a cure for this deadly disease.