DNA Damage Response and Mismatch Repair Gene Defects in Advanced and Metastatic Prostate Cancer.
Journal
Advances in anatomic pathology
ISSN: 1533-4031
Titre abrégé: Adv Anat Pathol
Pays: United States
ID NLM: 9435676
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
medline:
27
11
2023
pubmed:
27
11
2023
entrez:
27
11
2023
Statut:
aheadofprint
Résumé
Alterations in DNA damage response (DDR) and related genes are present in up to 25% of advanced prostate cancers (PCa). Most frequently altered genes are involved in the homologous recombination repair, the Fanconi anemia, and the mismatch repair pathways, and their deficiencies lead to a highly heterogeneous spectrum of DDR-deficient phenotypes. More than half of these alterations concern non-BRCA DDR genes. From a therapeutic perspective, poly-ADP-ribose polymerase inhibitors have demonstrated robust clinical efficacy in tumors with BRCA2 and BRCA1 alterations. Mismatch repair-deficient PCa, and a subset of CDK12-deficient PCa, are vulnerable to immune checkpoint inhibitors. Emerging data point to the efficacy of ATR inhibitors in PCa with ATM deficiencies. Still, therapeutic implications are insufficiently clarified for most of the non-BRCA DDR alterations, and no successful targeted treatment options have been established.
Identifiants
pubmed: 38008971
doi: 10.1097/PAP.0000000000000422
pii: 00125480-990000000-00079
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
M.A.R. is a co-inventor on patents in the area of diagnosis and therapy in prostate cancer for ETS fusions (University of Michigan and the Brigham and Women’s Hospital), SPOP mutations (Cornell University), and EZH2 (University of Michigan). The remaining authors have no funding or conflicts of interest to disclose.
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