Advances in PARP Inhibitors for Prostate Cancer
by
Steven Tisseverasinghe
1, 
Boris Bahoric
2, 
Maurice Anidjar
3,
Stephan Probst
4 and
Tamim Niazi
2,* 
1
Department of Radiation Oncology, McGill University, Gatineau, QC J8V 3R2, Canada
2
Department of Radiation Oncology, McGill University, Montreal, QC H3A 0G4, Canada
3
Department of Urology, McGill University, Montreal, QC H3A 0G4, Canada
4
Department of Nuclear Medicine, McGill University, Montreal, QC H3A 0G4, Canada
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(6), 1849; https://doi.org/10.3390/cancers15061849
Submission received: 6 February 2023
/
Revised: 12 March 2023
/
Accepted: 14 March 2023
/
Published: 20 March 2023
(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)
Simple Summary
Recent practice-changing trials have highlighted the importance of polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) in metastatic castrate resistant prostate cancer (mCRPC). PARP plays a quintessential role in repairing deoxyribonucleic acid (DNA) single-strand breaks by signaling and recruiting the necessary repair machinery to damaged areas. In mCRPC, where mutations are more likely to impair important repair pathways such as the homologous recombinational repair (HRR), remaining PARP repair pathways become critical to cell survival and can be exploited with targeted therapies. The purpose of our review was to compare and contrast recent pivotal trials in this setting and explore future avenues of research.
Abstract
Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer.
Keywords:
prostate cancer; PARP inhibitors; targeted therapy
