Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary tumor in children, adolescents and young adults. The primary tumor is initiated and driven by a single alteration in the DNA: A deletion of ~400kb that results in a fusion gene between the heat shock co-chaperone DNAJB1 and the catalytic subunit of protein kinase A, PRKACA. If the tumor is limited to the liver, then surgery is the accepted therapy. However, if the tumor has metastasized, there is no accepted therapy. Project 4 will develop therapeutics targeted to the fusion oncoprotein. It will use therapeutics to block the kinase activity of the oncoprotein and therapeutics to target the oncoprotein to the proteasome for destruction. The therapeutics will be tested on isolated protein, in dissociated cells from patient-derived xenografts, in human liver organoids of FLC and in mice with patient derived xenografts and in genetically engineered mouse models.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54CA243126-01
Application #
9834355
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065