Author Correction: Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer

PARP Inhibitors in Ovarian Cancer

Apoptosis is augmented in high-grade serous ovarian cancer by the combined inhibition of Bcl-2/Bcl-xL and PARP

The aim of our study was to evaluate possible synergistic cytotoxic effects of the combination treatment with the BH3-mimetic ABT-263 and the PARP inhibitor BMN 673 in high-grade serous ovarian cancer (HGSOC) cells using clinically achievable concentrations of each drug. In vitro cytotoxic effects of ABT-263 and BMN 673 were assessed by XTT assay in three HGSOC cell lines: OVCAR3, OVCAR8, and O...

Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.

PURPOSE PD-0332991 is a selective inhibitor of the CDK4/6 kinases with the ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. Here we investigate the role of CDK4/6 inhibition in human ovarian cancer. EXPERIMENTAL DESIGN We examined the effects of PD-0332991 on proliferation, cell-cycle, apoptosis, and Rb phosphorylation using a panel of 40 established human ovar...

PARP inhibition in epithelial ovarian cancer: high hopes undergo a reality check.

The treatment strategy of poly(ADP-ribose) polymerase (PARP) inhibition capitalizes on the inherent defect in homologous recombination that occurs in BRCA-deficient tumors by inhibiting the alternative DNA repair pathway involving base excision repair. Although PARP inhibitors were initially considered a potential treatment specifically for tumors with germline BRCA mutations, evidence of frequ...

CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer.

Immune checkpoint blockade has shown significant therapeutic efficacy in melanoma and other solid tumors, but results in ovarian cancer have been limited. With evidence that tumor immunogenicity modulates the response to checkpoint blockade, and data indicating that BRCA-deficient ovarian cancers express higher levels of immune response genes, we hypothesized that BRCA(-) ovarian tumors would b...