Genomic instability is one of the hallmarks of cancer. The incidence of genetic 
alterations in homologous recombination repair genes increases during cancer 
progression, and 20% of prostate cancers (PCas) have defects in DNA repair 
genes. Several somatic and germline gene alterations drive prostate cancer 
tumorigenesis, and the most important of these are BRCA2, BRCA1, ATM and CHEK2. 
There is a group of BRCAness tumours that share phenotypic and genotypic 
properties with classical BRCA-mutated tumours. Poly(ADP-ribose) polymerase 
inhibitors (PARPis) show synthetic lethality in cancer cells with impaired 
homologous recombination genes, and patients with these alterations are 
candidates for PARPi therapy. Androgen deprivation therapy is the mainstay of 
PCa therapy. PARPis decrease androgen signalling by interaction with molecular 
mechanisms of the androgen nuclear complex. The PROFOUND phase III trial, 
comparing olaparib with enzalutamide/abiraterone therapy, revealed increased 
radiological progression-free survival (rPFS) and overall survival (OS) among 
patients with metastatic castration-resistant prostate cancer (mCRPC) with 
BRCA1, BRCA2 or ATM mutations. The clinical efficacy of PARPis has been 
confirmed in ovarian, breast, pancreatic and recently also in a subset of PCa. 
There is growing evidence that molecular tumour boards are the future of the 
oncological therapeutic approach in prostate cancer. In this review, we 
summarise the data concerning the molecular mechanisms and preclinical and 
clinical data of PARPis in PCa.