Targeting DNA repair defects for precision medicine in prostate cancer
Author
Athie, Alejandro
Arce-Gallego, Sara
Gonzalez, Macarena
Morales-Barrera, Rafael
Suarez, Cristina
Casals Galobart, Teresa
Hernandez Viedma, Gonzalo
Carles, Joan
Mateo, Joaquin
Publication date
2019ISSN
1523-3790
Abstract
Purpose of Review: Genomic studies of localized and metastatic prostate cancer have identified a high prevalence of clinically actionable alterations including mutations in DNA repair genes. In this manuscript, we review the current knowledge on DNA repair defects in prostate cancer and provide an overview of how these alterations can be targeted towards a personalized prostate cancer management. Recent Findings: Twenty to 25% of metastatic prostate cancers harbor defects in DNA repair genes, most commonly in the homologous recombination genes. These defects confer increased sensitivity to platinum chemotherapy or poly (ADP-ribose) polymerase (PARP) inhibitors. Recent trials also support a synergistic effect of combining these therapies with androgen receptor-targeting agents. Identification of mismatch-repair defects could result in defining a prostate cancer population who may benefit from immune checkpoint inhibitors. These data have implications for family testing and early diagnosis, as many of these mutations are linked to inherited risk of prostate cancer. Summary: The DNA damage repair pathways are clinically relevant in prostate cancer, being a target for precision medicine; combination with standard-of-care androgen receptor (AR)-targeting agents may be synergistic.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Reparació de danys a l'ADN
Càncer de pròstata
PARP
BRCA1/2
Receptor d'andrògens
Alteracions genòmiques
Personalitzat medicament
Reparación de daños en el ADN
Cancer de prostata
PARP
BRCA1/2
Receptor de andrógenos
Alteraciones genómicas
Personalizado medicamento
DNA damage repair
Prostate cancer
PARP
BRCA1/2
Androgen receptor
Genomic alterations
Personalized medicine
Pages
10
Publisher
Springer Nature
Collection
21
Is part of
Current Oncology Reports
Citation
Athie, Alejandro; Arce-Gallego, Sara; Gonzalez, Macarena [et al.]. Targeting DNA repair defects for precision medicine in prostate cancer. Current Oncology Reports, 2019, 21, 42. Disponible en: <https://link.springer.com/article/10.1007/s11912-019-0790-6>. Fecha de acceso: 23 ene. 2024. DOI: 10.1007/s11912-019-0790-6
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- Ciències de la Salut [740]