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PARP Inhibitors in Epithelial Ovarian Cancer
Kristin N Taylor1, Ramez N Eskander1
1Rebecca and John Moores Cancer Center, Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California, San Diego, La Jolla, CA, United States.
Background:
Ovarian cancer remains the most common lethal gynecologic malignancy. The therapeutic gains with the use of traditional cytotoxic chemotherapy in advanced stage disease remain limited, reflecting the need for novel therapies. Poly(ADP-ribose) polymerase (PARP) inhibitors have recently demonstrated a significant therapeutic effect in patients with recurrent, high grade serous ovarian cancer, both in the treatment of existing disease and in prolonging the disease-free interval.
Objective:
The purpose of this article is to discuss PARP inhibitor use in patients with advanced stage ovarian cancer, and to extensively review the existing clinical literature and related patents.
Methods:
A comprehensive PUBMED literature review was conducted to identify all published phase 2 and phase 3 clinical trials involving PARP inhibitors in advanced epithelial ovarian cancer. Further, several patents related to PARP inhibitor use, companion diagnostic tests, and the development of biomarkers to predict PARP inhibitor responsiveness are described.
Results:
PARP inhibitors have demonstrated significant clinical activity in both BRCA deficient and wild-type patient cohorts, with all three FDA-approved PARP inhibitors demonstrating efficacy irrespective of BRCA mutation status in patients with advanced epithelial ovarian cancer.
Conclusion:
PARP inhibitors have emerged as an exciting new drug class in the treatment of epithelial ovarian cancer. Ongoing studies are aimed at improving our ability to identify ideal candidates for PARP inhibitor therapy, as well as to identify and target mechanisms of drug resistance, and novel combinatorial approaches.
Insights
Poly(ADP-ribose) polymerase (PARP) inhibitors show significant efficacy in treating advanced ovarian cancer, regardless of BRCA mutation status. These novel therapies offer improved treatment outcomes for patients with this lethal gynecologic malignancy.
Area of Science:
- Gynecologic Oncology
- Pharmacology
- Clinical Trials
Background:
- Ovarian cancer is a leading cause of cancer death in women.
- Traditional chemotherapy has limited efficacy in advanced stages.
- Novel therapies are needed for ovarian cancer treatment.
Purpose of the Study:
- To review the clinical literature and patents on Poly(ADP-ribose) polymerase (PARP) inhibitors in advanced ovarian cancer.
- To discuss the therapeutic role of PARP inhibitors in this patient population.
Main Methods:
- Comprehensive literature search of PubMed for Phase 2 and 3 clinical trials.
- Review of patents related to PARP inhibitors, diagnostics, and biomarkers.
Main Results:
- PARP inhibitors demonstrate significant clinical activity in advanced ovarian cancer.
- Efficacy is observed in both BRCA-deficient and BRCA wild-type patients.
- All FDA-approved PARP inhibitors show effectiveness regardless of BRCA mutation status.
Conclusions:
- PARP inhibitors represent a promising new drug class for epithelial ovarian cancer.
- Future research focuses on identifying ideal candidates, overcoming resistance, and exploring combinations.
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