PARP Inhibition, a New Therapeutic Avenue in Patients with Prostate Cancer.

Up to 25% of patients with metastatic prostate cancer present with germline or somatic DNA damage repair alterations, some of which are associated with aggressive disease and poor outcomes. New data have brought poly(ADP-ribose) polymerase (PARP) inhibitors into sharp focus in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Olaparib improved survival after at least one new hormonal therapy (NHT) in a cohort of patients harboring BRCA1, BRCA2 or ATM mutations in the PROfound trial, while rucaparib, talazoparib and niraparib demonstrated compelling activity in phase II trials. While patients with prostate cancer and BRCA1 or BRCA2 mutations may derive greatest benefit of PARP inhibition, the magnitude of benefit seems much lower in the context of most other homologous recombination gene mutations. Several PARP inhibitors are currently developed in combination with conventional therapy, including chemotherapy, NHT, and alpha-particle emitters, at different disease stages. Herein, we review the rationale for PARP inhibition in patients with prostate cancer, discuss the impact of PARP inhibitors on outcomes, and explore underlying challenges for future developments.

Drugs. 2022 May 05 [Epub ahead of print]

Ronan Flippot, Anna Patrikidou, Mihaela Aldea, Emeline Colomba, Pernelle Lavaud, Laurence Albig├Ęs, Natacha Naoun, Pierre Blanchard, Mario Terlizzi, Camilo Garcia, Alice Bernard-Tessier, Alina Fuerea, Mario Di Palma, Bernard Escudier, Yohann Loriot, Giulia Baciarello, Karim Fizazi

Department of Cancer Medicine, Paris Saclay University, Gustave Roussy, 114 rue Edouard Vaillant, 94 800, Villejuif, France., Department of Radiation Oncology, Paris Saclay University, Gustave Roussy, Villejuif, France., Department of Nuclear Medicine, Paris Saclay University, Gustave Roussy, Villejuif, France., Istituto Nazionale dei Tumori, Milan, Italy., Department of Cancer Medicine, Paris Saclay University, Gustave Roussy, 114 rue Edouard Vaillant, 94 800, Villejuif, France. .

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