FCF Funded Projects

Developing therapeutics for fibrolamellar hepatocellular carcinoma

Status: Completed

Timeframe: 2016 – 2017

Goal: Develop new therapeutics for FLC

Principal Investigator: Sandy Simon, Ph.D., Professor
Investigator Collaboration: Barbara A. Lyons, Ph.D., Professor, New Mexico State University

The goal of this work was to develop therapeutics for FLC. The team identified three independent strategies based on their laboratory’s work showing that a single common DNA alteration is found in all fibrolamellar tumors leading to the DNAJB1-PRKACA fusion and that this chimera is sufficient to cause fibrolamellar. The three projects covered included:

  1. A high-throughput screen for molecules that directly block the chimera (covering millions of compounds with no prior assumptions about which compounds might work).
  2. A screen to identify molecules that are directly phosphorylated by the chimera.
  3. An analysis of the structural dynamics of the chimera using a molecular dynamics simulation to identify sites on the chimera that would be appropriate for targeting therapeutics.