Despite remarkable progress in the last decade, metastatic prostate cancer (mPCa) remains incurable. The approval of PARP inhibitors (PARPis) represents a milestone in this field, which definitively enters the era of precision medicine, as mPCa is often enriched for defects of homologous recombination repair genes. PARPis are now used as single agents for patients with metastatic castration-resistant PCa. Moreover, combinations of PARPis plus androgen-receptor targeted agents and immune checkpoint inhibitors, and earlier applications of PARPis in the metastatic hormone-sensitive PCa are under evaluation, representing the possible upcoming applications of these agents. Mechanisms of sensitization and resistance have been only partially elucidated. In our review, we summarize the current clinical evidence regarding PARPis in mPCa and the future directions of these targeted agents.
Critical reviews in oncology/hematology. 2023 Oct 18 [Epub ahead of print]
Brigida Anna Maiorano, Vincenza Conteduca, Martina Catalano, Lorenzo Antonuzzo, Evaristo Maiello, Ugo De Giorgi, Giandomenico Roviello
Oncology Unit, IRCCS Foundation Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. Electronic address: ., Department of Medical and Surgical Sciences, Unit of Medical Oncology and Biomolecular Therapy, University of Foggia, Policlinico Riuniti, Foggia, Italy., Department of Health Sciences, University of Florence, Florence, Italy., Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Clinical Oncology Unit, and Medical Oncology Unit, Careggi University Hospital, Florence, Italy., Oncology Unit, IRCCS Foundation Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy., Department of Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.