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Published on: February 24, 2023
Therapeutic applications of PARP inhibitors in ovarian cancer
Hongyu Xie1, Wenjie Wang2, Bairong Xia1
1Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, PR China.
Abstract:
Ovarian cancer is the most lethal gynecologic malignancy with a high recurrence rate. Poly(ADP-ribose) polymerase inhibitors (PARPi) are one of the most active new therapies for treatment of ovarian cancer. These treatment modalities are based on the mechanisms of "synthetic lethal" and "PARP trapping", especially for patients with homologous recombination deficiencies, and they demonstrate a high survival advantage. However, resistance to PARPi is an emerging problem. Identifying potential biomarkers to monitor the resistance and developing drug combination strategies are effective ways to address PARPi resistance. This review introduces the mechanisms of anticancer activity of PARPi and the developmental history in clinical research. Moreover, this paper systematically analyzes the functions of PARP family proteins. Additionally, this work highlights the treatment prospects of the combination of immunotherapy and PARPi in ovarian cancer. Finally, we propose several novel technologies to overcome the limitations of current preclinical studies and utilize them to select potential targets for combined drug therapy and identify biomarkers of PARPi resistance in ovarian cancer.
Insights
Poly(ADP-ribose) polymerase inhibitors (PARPi) show promise for ovarian cancer, but resistance is a challenge. This review explores PARPi mechanisms, resistance, and combinations with immunotherapy to improve patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Ovarian cancer is a deadly gynecologic malignancy with frequent recurrence.
- Poly(ADP-ribose) polymerase inhibitors (PARPi) offer a novel therapeutic approach based on synthetic lethality and PARP trapping.
- PARPi demonstrate significant survival benefits, particularly in patients with homologous recombination deficiencies.
Purpose of the Study:
- To review the mechanisms and clinical development of PARPi in ovarian cancer.
- To analyze the functions of PARP family proteins.
- To explore strategies for overcoming PARPi resistance, including drug combinations and biomarker identification.
Main Methods:
- Literature review of PARPi mechanisms, clinical trials, and resistance pathways.
- Systematic analysis of PARP family protein functions.
- Discussion of novel technologies for preclinical studies and target selection.
Main Results:
- PARPi exhibit potent anticancer activity through synthetic lethality and PARP trapping.
- Emerging resistance to PARPi necessitates the development of new therapeutic strategies.
- Combination therapy, particularly with immunotherapy, shows promise for enhancing treatment efficacy.
Conclusions:
- Understanding PARPi mechanisms and resistance is crucial for effective ovarian cancer treatment.
- Identifying biomarkers and developing combination therapies are key to overcoming PARPi resistance.
- Novel technologies can advance preclinical research and identify new therapeutic targets and biomarkers.
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