Evaluation of Protein Kinase cAMP-Activated Catalytic Subunit Alpha as a Therapeutic Target for Fibrolamellar Carcinoma.

ABSTRACT:

Background and aims

Fibrolamellar carcinoma (FLC) is a rare, difficult-to-treat liver cancer primarily affecting pediatric and adolescent patients, and for which precision medicine approaches have historically not been possible. The DNAJB1-PRKACA gene fusion was identified as a driver of FLC pathogenesis. We aimed to assess whether FLC tumors maintain dependency on this gene fusion and determine if PRKACA is a viable therapeutic target.

Methods

FLC patient-derived xenograft (PDX) shRNA cell lines were implanted subcutaneously into female NOD-SCID mice and tumors were allowed to develop prior to randomization to doxycycline (to induce knockdown) or control groups. Tumor development was assessed every 2 days. To assess the effect of treatment with novel selective PRKACA

SUBMITTER: Schalm SS 

PROVIDER: S-EPMC11307690 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature