FCF Funded Projects

Characterizing enzyme inhibition of the DnaJPKAc chimeric protein derived from fibrolamellar hepatocellular carcinomas

Status: Completed

Timeframe: 2017 – 2019

Goal: Characterize inhibition of the DnaJ-PKAc chimeric protein in fibrolamellar carcinoma

Principal Investigator: Hibba tul Rehman, M.D., University of Vermont

The DNAJB1-PRKACA fusion gene produces the DnaJ-PKAc fusion kinase protein, which is present in nearly all FLC tumors and promotes liver tumor formation in mice. Kinases, including fusion kinases, have been successful drug targets in numerous cancer types. Inhibition of DnaJ-PKAc may provide the first targeted therapy for FLC. This study proposed a two pronged approach towards identifying therapeutic inhibitors of the fusion:

  1. Screening a previously developed peptide library to identify peptides that preferentially bind chimeric DnaJ-PKAc over normal, wide-type protein in vitro.
  2. Developing a library of inhibitory peptides that would preferentially inhibit DnaJ-PKAc.

These aim of these efforts was to develop an understanding that will support the development of inhibitors that regulate the function of the chimeric kinase without affecting the wild-type kinase, thus selectively targeting cancer cells without affecting healthy tissue.