dc.contributor.author | Mateo, J | |
dc.contributor.author | Boysen, G | |
dc.contributor.author | Barbieri, CE | |
dc.contributor.author | Bryant, HE | |
dc.contributor.author | Castro, E | |
dc.contributor.author | Nelson, PS | |
dc.contributor.author | Olmos, D | |
dc.contributor.author | Pritchard, CC | |
dc.contributor.author | Rubin, MA | |
dc.contributor.author | de Bono, JS | |
dc.date.accessioned | 2017-01-05T17:03:44Z | |
dc.date.issued | 2017-03-01 | |
dc.identifier.citation | European urology, 2017, 71 (3), pp. 417 - 425 | |
dc.identifier.issn | 0302-2838 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/377 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.doi | 10.1016/j.eururo.2016.08.037 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 417 - 425 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE BV | |
dc.subject | Humans | |
dc.subject | Prostatic Neoplasms | |
dc.subject | BRCA1 Protein | |
dc.subject | BRCA2 Protein | |
dc.subject | Prognosis | |
dc.subject | Molecular Diagnostic Techniques | |
dc.subject | DNA Repair | |
dc.subject | Male | |
dc.subject | MutS Homolog 2 Protein | |
dc.subject | DNA Mismatch Repair | |
dc.subject | Recombinational DNA Repair | |
dc.subject | Ataxia Telangiectasia Mutated Proteins | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.subject | Poly(ADP-ribose) Polymerase Inhibitors | |
dc.subject | Precision Medicine | |
dc.subject | MutL Protein Homolog 1 | |
dc.title | DNA Repair in Prostate Cancer: Biology and Clinical Implications. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-08-12 | |
rioxxterms.versionofrecord | 10.1016/j.eururo.2016.08.037 | |
rioxxterms.licenseref.startdate | 2017-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | European urology | |
pubs.issue | 3 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 71 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | De Bono, Johann | |