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PARP inhibitors in advanced prostate cancer: when to use them?
- Source :
- Endocrine-Related Cancer. 28:T79-T93
- Publication Year :
- 2021
- Publisher :
- Bioscientifica, 2021.
-
Abstract
- Poly (ADP-ribose) polymerase (PARP) inhibitors have antitumor activity in advanced prostate cancer associated with loss of homologous recombination repair (HRR) function. About 20% of all patients with advanced prostate cancer present germline or tumor mutations in HRR-related genes, the most common being BRCA2, mutated in approximately 10% of all advanced prostate cancers. Challenges related to sample availability, tumor heterogeneity and access to NGS technology need to be addressed for a successful implementation of genomic stratification in routine clinical practice. The recent regulatory approvals of PARP inhibitors olaparib and rucaparib represent the first molecular biomarker-guided drugs for men with prostate cancer. While these findings represent a significant advance in the field of precision medicine and prostate cancer, there are still many unsolved questions on the optimal use of PARP inhibitors in this disease. Several clinical trials have shown that different mutations in various genes are associated with distinct magnitudes of sensitivity to PARP inhibitors, with BRCA2 mutations associating with more frequent and durable responses, questioning the benefit for subset of patients with mutations in other HRR-associated genes. In this review, we scrutinize the clinical development of different PARP inhibitors for the treatment of advanced prostate cancer, and we discuss how the study of additional biomarkers and the design of rational drug combinations can maximize patient benefit from this drug class.
- Subjects :
- Male
Oncology
Cancer Research
medicine.medical_specialty
DNA Repair
Endocrinology, Diabetes and Metabolism
Disease
Poly(ADP-ribose) Polymerase Inhibitors
Olaparib
chemistry.chemical_compound
Prostate cancer
Endocrinology
Prostate
Internal medicine
Humans
Medicine
Liquid biopsy
Rucaparib
business.industry
Prostatic Neoplasms
Precision medicine
medicine.disease
Clinical trial
medicine.anatomical_structure
chemistry
Mutation
Poly(ADP-ribose) Polymerases
business
Subjects
Details
- ISSN :
- 14796821 and 13510088
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Endocrine-Related Cancer
- Accession number :
- edsair.doi.dedup.....2d7faada0e85e5747ce048893ef4dd04