{"entity":{"id":"parp-plus-arpi","kind":"pairing","name":"PARP inhibitor + AR pathway inhibitor (prostate)","aka":[],"tldr":"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.","asOf":"2026-09-04","links":[{"label":"PROpel: abiraterone and olaparib for metastatic castration-resistant prostate cancer (NEJM Evidence 2022)","url":"https://doi.org/10.1056/EVIDoa2200043"},{"label":"TALAPRO-2: talazoparib plus enzalutamide in first-line metastatic castration-resistant prostate cancer (Lancet 2023)","url":"https://doi.org/10.1016/S0140-6736(23)01055-3"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["olaparib","talazoparib","niraparib"],"companies":[],"institutions":[],"pathways":["ddr","ar-signaling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-clarke-nejm-evid"],"journals":[],"dependsOn":[],"notes":[],"a":"parp-inhibitor","b":"androgen-deprivation","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.","pairingType":"combination"},"route":"/pairings/parp-plus-arpi/","neighbours":{"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"drug":[{"id":"niraparib","kind":"drug","name":"Niraparib","route":"/drugs/niraparib/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"talazoparib","kind":"drug","name":"Talazoparib","route":"/drugs/talazoparib/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"}],"paper":[{"id":"paper-clarke-nejm-evid","kind":"paper","name":"Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer","route":"/key-papers/paper-clarke-nejm-evid/"}],"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"}]}}