BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations
Prostate cancer ranks fifth in cancer-related mortality in men worldwide. DNA damage is implicated in cancer and DNA damage response (DDR) pathways are in place against this to maintain genomic stability. Impaired DDR pathways play a role in prostate carcinogenesis and germline or somatic mutations...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12628 |
| _version_ | 1797507789481836544 |
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| author | Sidrah Shah Rachelle Rachmat Synthia Enyioma Aruni Ghose Antonios Revythis Stergios Boussios |
| author_facet | Sidrah Shah Rachelle Rachmat Synthia Enyioma Aruni Ghose Antonios Revythis Stergios Boussios |
| author_sort | Sidrah Shah |
| collection | DOAJ |
| description | Prostate cancer ranks fifth in cancer-related mortality in men worldwide. DNA damage is implicated in cancer and DNA damage response (DDR) pathways are in place against this to maintain genomic stability. Impaired DDR pathways play a role in prostate carcinogenesis and germline or somatic mutations in DDR genes have been found in both primary and metastatic prostate cancer. Among these, <i>BRCA</i> mutations have been found to be especially clinically relevant with a role for germline or somatic testing. Prostate cancer with DDR defects may be sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors which target proteins in a process called PARylation. Initially they were used to target BRCA-mutated tumor cells in a process of synthetic lethality. However, recent studies have found potential for PARP inhibitors in a variety of other genetic settings. In this review, we explore the mechanisms of DNA repair, potential for genomic analysis of prostate cancer and therapeutics of PARP inhibitors along with their safety profile. |
| first_indexed | 2024-03-10T04:53:26Z |
| format | Article |
| id | doaj.art-8caf0124fbba404088b59cabe4164121 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:53:26Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8caf0124fbba404088b59cabe41641212023-11-23T02:25:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231262810.3390/ijms222312628BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment ConsiderationsSidrah Shah0Rachelle Rachmat1Synthia Enyioma2Aruni Ghose3Antonios Revythis4Stergios Boussios5Department of Palliative Care, Guy’s and St Thomas’ Hospital, Great Maze Pond, London SE1 9RT, UKDepartment of Radiology, Guy’s and St Thomas’ Hospital, Great Maze Pond, London SE1 9RT, UKDepartment of Medical Oncology, Medway NHS Foundation Trust, Windmill Road, Gillingham ME7 5NY, UKDepartment of Medical Oncology, Barts Cancer Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, W Smithfield, London EC1A 7BE, UKDepartment of Medical Oncology, Medway NHS Foundation Trust, Windmill Road, Gillingham ME7 5NY, UKDepartment of Medical Oncology, Medway NHS Foundation Trust, Windmill Road, Gillingham ME7 5NY, UKProstate cancer ranks fifth in cancer-related mortality in men worldwide. DNA damage is implicated in cancer and DNA damage response (DDR) pathways are in place against this to maintain genomic stability. Impaired DDR pathways play a role in prostate carcinogenesis and germline or somatic mutations in DDR genes have been found in both primary and metastatic prostate cancer. Among these, <i>BRCA</i> mutations have been found to be especially clinically relevant with a role for germline or somatic testing. Prostate cancer with DDR defects may be sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors which target proteins in a process called PARylation. Initially they were used to target BRCA-mutated tumor cells in a process of synthetic lethality. However, recent studies have found potential for PARP inhibitors in a variety of other genetic settings. In this review, we explore the mechanisms of DNA repair, potential for genomic analysis of prostate cancer and therapeutics of PARP inhibitors along with their safety profile.https://www.mdpi.com/1422-0067/22/23/12628prostate cancerDNA damage repair<i>BRCA</i> mutationsPARP inhibitors |
| spellingShingle | Sidrah Shah Rachelle Rachmat Synthia Enyioma Aruni Ghose Antonios Revythis Stergios Boussios BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations International Journal of Molecular Sciences prostate cancer DNA damage repair <i>BRCA</i> mutations PARP inhibitors |
| title | BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations |
| title_full | BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations |
| title_fullStr | BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations |
| title_full_unstemmed | BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations |
| title_short | BRCA Mutations in Prostate Cancer: Assessment, Implications and Treatment Considerations |
| title_sort | brca mutations in prostate cancer assessment implications and treatment considerations |
| topic | prostate cancer DNA damage repair <i>BRCA</i> mutations PARP inhibitors |
| url | https://www.mdpi.com/1422-0067/22/23/12628 |
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