# PARP inhibitor + AR pathway inhibitor (prostate)

Source: https://onco.cc/pairings/parp-plus-arpi/  
OnCo record `parp-plus-arpi` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In prostate cancer, blocking androgen signalling makes cells more dependent on PARP, and PARP inhibition weakens AR signalling in turn.

## Summary

This combination pairs PARP inhibitors with Androgen deprivation & AR pathway inhibitors in Prostate cancer. The mechanism is bidirectional cross-talk: the androgen receptor regulates DNA repair genes and PARP is an AR co-factor, so blocking androgen signalling makes cells more dependent on PARP while PARP inhibition weakens AR signalling, creating synergy that extends beyond BRCA-mutant tumours and linking the DNA damage response & homologous recombination and Androgen receptor signalling pathways. Three phase 3 trials support it: PROpel (Olaparib with abiraterone), TALAPRO-2 (Talazoparib with enzalutamide, which showed an overall survival benefit) and MAGNITUDE (Niraparib with abiraterone). The benefit is largest in HRR-mutant tumours and present in some all-comer analyses.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: PARP inhibitors + Androgen deprivation & AR pathway inhibitors
- Type: combination
- Rationale: AR regulates DNA repair genes; PARP is an AR co-factor. Bidirectional cross-talk creates synergy beyond BRCA-mutant tumours.
- Evidence: Three phase 3 trials, OS benefit in TALAPRO-2.

## Sources

- PROpel: abiraterone and olaparib for metastatic castration-resistant prostate cancer (NEJM Evidence 2022): https://doi.org/10.1056/EVIDoa2200043
- TALAPRO-2: talazoparib plus enzalutamide in first-line metastatic castration-resistant prostate cancer (Lancet 2023): https://doi.org/10.1016/S0140-6736(23)01055-3

## Connected records

- cancers: [Prostate cancer](https://onco.cc/cancers/prostate/)
- drugs: [Niraparib](https://onco.cc/drugs/niraparib/), [Olaparib](https://onco.cc/drugs/olaparib/), [Talazoparib](https://onco.cc/drugs/talazoparib/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/)
- key papers: [Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer](https://onco.cc/key-papers/paper-clarke-nejm-evid/)
- technologies: [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/)

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