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Title: Molecular pathways: targeting DNA repair pathway defects enriched in metastasis.
Authors: Corcoran, Niall
Clarkson, Michael
Stuchbery, Ryan
Hovens, Christopher
Keywords: DNA
DNA Damage Repair Genes
DDR Genes
DDR Pathways
DNA Errors
TP53 Protein
PARP Enzyme
Cancer Treatment
Australian Prostate Cancer Research Centre, Epworth HealthCare, Victoria, Australia
Issue Date: Jul-2016
Publisher: American Association for Cancer Research
Citation: Clin Cancer Res. 2016 Jul 1;22(13):3132-3137
Abstract: The maintenance of a pristine genome, free from errors, is necessary to prevent cellular transformation and degeneration. When errors in DNA are detected, DNA damage repair (DDR) genes and their regulators are activated to effect repair. When these DDR pathways are themselves mutated or aberrantly downregulated, cancer and neurodegenerative disorders can ensue. Multiple lines of evidence now indicate, however, that defects in key regulators of DNA repair pathways are highly enriched in human metastasis specimens and hence may be a key step in the acquisition of metastasis and the ability of localized disease to disseminate. Some of the key regulators of checkpoints in the DNA damage response are the TP53 protein and the PARP enzyme family. Targeting of these pathways, especially through PARP inhibition, is now being exploited therapeutically to effect significant clinical responses in subsets of individuals, particularly in patients with ovarian cancer or prostate cancer, including cancers with a marked metastatic burden. Targeting DNA repair-deficient tumors with drugs that take advantage of the fundamental differences between normal repair-proficient cells and repair-deficient tumors offers new avenues for treating advanced disease in the future.
DOI: 10.1158/1078-0432.CCR-15-1050
PubMed URL:
ISSN: 1078-0432
Journal Title: Clinical Cancer Research
Type: Journal Article
Affiliated Organisations: Department of Surgery, Division of Urology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
University of Melbourne, Melbourne, Victoria, Australia
Appears in Collections:Cancer Services
Epworth Prostate Centre
UroRenal, Vascular

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