Combined inhibition of BADSer99 phosphorylation and PARP ablates models of recurrent ovarian carcinoma.

ABSTRACT:

Background

Poly (ADP-ribose) polymerase inhibitors (PARPis) have been approved for the treatment of recurrent epithelial ovarian cancer (EOC), regardless of BRCA status or homologous recombination repair deficiency. However, the low response of platinum-resistant EOC, the emergence of resistance in BRCA-deficient cancer, and therapy-associated toxicities in patients limit the clinical utility of PARPis in recurrent EOC.

Methods

The association of phosphorylated (p) BADS99 with clinicopathological parameters and survival outcomes in an EOC cohort was assessed by immunohistochemistry. The therapeutic synergy, and mechanisms thereof, between a pBADS99 inhibitor and PARPis in EOC was determined in vitro and in vivo using cell line and patient-derived models.

Res

SUBMITTER: Zhang X 

PROVIDER: S-EPMC9250505 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature