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DNA Repair in Prostate Cancer: Biology and Clinical Implications.

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Date
2017-03
ICR Author
De Bono, Johann
Marsden,
Mateo Valderrama, Joaquin
Author
Mateo, J
Boysen, G
Barbieri, CE
Bryant, HE
Castro, E
Nelson, PS
Olmos, D
Pritchard, CC
Rubin, MA
de Bono, JS
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Type
Journal Article
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Abstract
Context For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification.Objective To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease.Evidence acquisition A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer.Evidence synthesis We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC.Conclusions Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies.Patient summary Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed.
URI
https://repository.icr.ac.uk/handle/internal/377
DOI
https://doi.org/10.1016/j.eururo.2016.08.037
Collections
  • Clinical Studies
Subject
Humans
Prostatic Neoplasms
BRCA1 Protein
BRCA2 Protein
Prognosis
Molecular Diagnostic Techniques
DNA Repair
Male
MutS Homolog 2 Protein
DNA Mismatch Repair
Recombinational DNA Repair
Ataxia Telangiectasia Mutated Proteins
Prostatic Neoplasms, Castration-Resistant
Poly(ADP-ribose) Polymerase Inhibitors
Precision Medicine
MutL Protein Homolog 1
Research team
Prostate Cancer Targeted Therapy Group
Language
eng
Date accepted
2016-08-12
License start date
2017-03
Citation
European urology, 2017, 71 (3), pp. 417 - 425

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