DNA Repair in Prostate Cancer: Biology and Clinical Implications.

Mateo, Joaquin; Boysen, Gunther; Barbieri, Christopher E; Bryant, Helen E; Castro, Elena; Nelson, Pete S; Olmos, David; Pritchard, Colin C; Rubin, Mark Andrew; de Bono, Johann S (2017). DNA Repair in Prostate Cancer: Biology and Clinical Implications. European urology, 71(3), pp. 417-425. Elsevier 10.1016/j.eururo.2016.08.037

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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.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

UniBE Contributor:

Rubin, Mark Andrew

Subjects:

500 Science
500 Science > 570 Life sciences; biology

ISSN:

0302-2838

Publisher:

Elsevier

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

22 Feb 2018 09:50

Last Modified:

04 Nov 2019 19:35

Publisher DOI:

10.1016/j.eururo.2016.08.037

PubMed ID:

27590317

Uncontrolled Keywords:

BRCA DNA damage DNA repair PARP Personalized medicine Prostate cancer

BORIS DOI:

10.7892/boris.110868

URI:

https://boris.unibe.ch/id/eprint/110868

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