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Review
. 2022 Jun 15;10(6):1416.
doi: 10.3390/biomedicines10061416.

PARP Inhibitors: A New Horizon for Patients with Prostate Cancer

Belén Congregado  1 , Inés Rivero  1 , Ignacio Osmán  1 , Carmen Sáez  2 , Rafael Medina López  1
Affiliations
Review

PARP Inhibitors: A New Horizon for Patients with Prostate Cancer

Belén Congregado et al. Biomedicines. .

Abstract

The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In addition, it is also the first time that genetic mutation tests have been included in the therapeutic algorithm of this disease, representing a significant step forward for precision and personalized treatment of prostate cancer. The objectives of this review are: (1) understanding the mechanism of action of PARPi in monotherapy and combinations; (2) gaining insights on patient selection for PARPi; (3) exposing the pivotal studies that have allowed its approval, and; (4) offering an overview of the ongoing trials. Nevertheless, many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use PARPi in monotherapy or in combination, and when is the best time to use them in advanced or localized disease. To answer these and other questions, many clinical trials are underway. Some of them have recently demonstrated promising results that may favor the introduction of new combinations in metastatic castration-resistant prostate cancer.

Keywords: PARP inhibitors; mutation test; prostate cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Simple scheme of Synthetic Lethality. The alteration of either gene alone (gen I or gen II) does not causes cell death, while the simultaneous alteration of two genes triggers cell death. In cancer treatment, gene II becomes a therapeutic target that can be used to attack tumor cells with dysfunction in I.
Figure 2
Figure 2
PARPi antitumor activity based on Synthetic Lethality. I: Normal cell. Excision repair base (ERB) and homologous recombination (HR) are functional: repair DNA maintaining cell viability. II, III: Through BRCA mutation or PARPi, one of the repair pathway’s is inhibited. Once the other pathway is functional, the cell maintains its viability. IV: Both DNA repair pathways are inhibited; therefore, errors in the DNA are not repaired, resulting in cell death.
Figure 3
Figure 3
PARPi Trapping Potency.
See this image and copyright information in PMC

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