Poly(Adenosine Diphosphate Ribose) Polymerase (PARP) Inhibitors in the Treatment of Advanced Ovarian Cancer: A Narrative Review

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2024 Oct 3

PMID 39360040

Authors

Deepika Dewani

Arpita Jaiswal

Pravin Karwade

Affiliations

Soon will be listed here.

Abstract

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have appeared as a revolutionary approach to treating advanced ovarian cancer, particularly in patients with breast cancer (BRCA) mutations and homologous recombination deficiency (HRD). This narrative review explores PARP inhibitors' clinical efficiency, safety, and changing role in this context. PARP inhibitors, such as olaparib, niraparib, or rucaparib, provide considerable benefits regarding progression-free survival expansion and overall outcomes improvement in first-line maintenance and recurrent settings. The underlying mechanisms, patient selection criteria, and resistance patterns are discussed, alongside insights into combination therapies to overcome resistance and enhance therapeutic efficacy. Ongoing clinical trials and future potential for personalized therapy approaches using PARP inhibitors for advanced ovarian cancer are also highlighted. However, despite these drugs' phenomenal ability to revolutionize treatment protocols for such cancer types, several challenges remain: toxicity management, cost, and development of resistance will require more research to optimize their use or broaden patient populations who can benefit from them.

References

OCearbhaill R . Using PARP Inhibitors in Advanced Ovarian Cancer. Oncology (Williston Park). 2018; 32(7):339-43. PMC: 6662180. View

Cordani N, Bianchi T, Ammoni L, Cortinovis D, Cazzaniga M, Lissoni A . An Overview of PARP Resistance in Ovarian Cancer from a Molecular and Clinical Perspective. Int J Mol Sci. 2023; 24(15). PMC: 10418869. DOI: 10.3390/ijms241511890. View

Veneziani A, Scott C, Wakefield M, Tinker A, Lheureux S . Fighting resistance: post-PARP inhibitor treatment strategies in ovarian cancer. Ther Adv Med Oncol. 2023; 15:17588359231157644. PMC: 9983116. DOI: 10.1177/17588359231157644. View

Soung Y, Chung J . Combination Treatment Strategies to Overcome PARP Inhibitor Resistance. Biomolecules. 2023; 13(10). PMC: 10604269. DOI: 10.3390/biom13101480. View

Colombo I, Lheureux S, Oza A . Rucaparib: a novel PARP inhibitor for advanced ovarian cancer. Drug Des Devel Ther. 2018; 12:605-617. PMC: 5868608. DOI: 10.2147/DDDT.S130809. View

Garg V, Oza A . Treatment of Ovarian Cancer Beyond PARP Inhibition: Current and Future Options. Drugs. 2023; 83(15):1365-1385. PMC: 10581945. DOI: 10.1007/s40265-023-01934-0. View

Banerjee S, Gonzalez-Martin A, Harter P, Lorusso D, Moore K, Oaknin A . First-line PARP inhibitors in ovarian cancer: summary of an round-table discussion. ESMO Open. 2020; 5(6):e001110. PMC: 7783599. DOI: 10.1136/esmoopen-2020-001110. View

Bound N, Vandenberg C, Kartikasari A, Plebanski M, Scott C . Improving PARP inhibitor efficacy in high-grade serous ovarian carcinoma: A focus on the immune system. Front Genet. 2022; 13:886170. PMC: 9505691. DOI: 10.3389/fgene.2022.886170. View

Li X, Heyer W . Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 2008; 18(1):99-113. PMC: 3087377. DOI: 10.1038/cr.2008.1. View

10.

Faraoni I, Graziani G . Role of BRCA Mutations in Cancer Treatment with Poly(ADP-ribose) Polymerase (PARP) Inhibitors. Cancers (Basel). 2018; 10(12). PMC: 6316750. DOI: 10.3390/cancers10120487. View

11.

Dedes K, Wilkerson P, Wetterskog D, Weigelt B, Ashworth A, Reis-Filho J . Synthetic lethality of PARP inhibition in cancers lacking BRCA1 and BRCA2 mutations. Cell Cycle. 2011; 10(8):1192-9. PMC: 3117132. DOI: 10.4161/cc.10.8.15273. View

12.

Prakash R, Zhang Y, Feng W, Jasin M . Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb Perspect Biol. 2015; 7(4):a016600. PMC: 4382744. DOI: 10.1101/cshperspect.a016600. View

13.

Slade D . PARP and PARG inhibitors in cancer treatment. Genes Dev. 2020; 34(5-6):360-394. PMC: 7050487. DOI: 10.1101/gad.334516.119. View

14.

Mangogna A, Munari G, Pepe F, Maffii E, Giampaolino P, Ricci G . Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches. J Pers Med. 2023; 13(2). PMC: 9968181. DOI: 10.3390/jpm13020284. View

15.

Purwar R, Ranjan R, Pal M, Upadhyay S, Kumar T, Pandey M . Role of PARP inhibitors beyond BRCA mutation and platinum sensitivity in epithelial ovarian cancer: a meta-analysis of hazard ratios from randomized clinical trials. World J Surg Oncol. 2023; 21(1):157. PMC: 10204292. DOI: 10.1186/s12957-023-03027-4. View

16.

Valabrega G, Scotto G, Tuninetti V, Pani A, Scaglione F . Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy. Int J Mol Sci. 2021; 22(8). PMC: 8073512. DOI: 10.3390/ijms22084203. View

17.

Neiger H, Siegler E, Shi Y . Breast Cancer Predisposition Genes and Synthetic Lethality. Int J Mol Sci. 2021; 22(11). PMC: 8198377. DOI: 10.3390/ijms22115614. View

18.

Morales J, Li L, Fattah F, Dong Y, Bey E, Patel M . Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit Rev Eukaryot Gene Expr. 2014; 24(1):15-28. PMC: 4806654. DOI: 10.1615/critreveukaryotgeneexpr.2013006875. View

19.

Bhamidipati D, Haro-Silerio J, Yap T, Ngoi N . PARP inhibitors: enhancing efficacy through rational combinations. Br J Cancer. 2023; 129(6):904-916. PMC: 10491787. DOI: 10.1038/s41416-023-02326-7. View

20.

Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H . Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health. 2019; 11:287-299. PMC: 6500433. DOI: 10.2147/IJWH.S197604. View