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dc.contributor.authorMinchom, Aen_US
dc.contributor.authorAversa, Cen_US
dc.contributor.authorLopez, Jen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2019-02-25T16:08:32Z
dc.date.issued2018en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30023007en_US
dc.identifier10.1177_1758835918786658en_US
dc.identifier.citationTher Adv Med Oncol, 2018, 10 pp. 1758835918786658 - ?en_US
dc.identifier.issn1758-8340en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3085
dc.identifier.doi10.1177/1758835918786658en_US
dc.description.abstractMaintenance of genomic stability is a critical determinant of cell survival and relies on the coordinated action of the DNA damage response (DDR), which orchestrates a network of cellular processes, including DNA replication, DNA repair and cell-cycle progression. In cancer, the critical balance between the loss of genomic stability in malignant cells and the DDR provides exciting therapeutic opportunities. Drugs targeting DDR pathways taking advantage of clinical synthetic lethality have already shown therapeutic benefit - for example, the PARP inhibitor olaparib has shown benefit in BRCA-mutant ovarian and breast cancer. Olaparib has also shown benefit in metastatic prostate cancer in DDR-defective patients, expanding the potential biomarker of response beyond BRCA. Other agents and combinations aiming to block the DDR while pushing damaged DNA through the cell cycle, including PARP, ATR, ATM, CHK and DNA-PK inhibitors, are in development. Emerging work is also uncovering how the DDR interacts intimately with the host immune response, including by activating the innate immune response, further suggesting that clinical applications together with immunotherapy may be beneficial. Here, we review recent considerations related to the DDR from a clinical standpoint, providing a framework to address future directions and clinical opportunities.en_US
dc.format.extent1758835918786658 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectDNA damage responseen_US
dc.subjectPARP inhibitorsen_US
dc.subjectimmunotherapyen_US
dc.titleDancing with the DNA damage response: next-generation anti-cancer therapeutic strategies.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-06-08en_US
rioxxterms.versionofrecord10.1177/1758835918786658en_US
rioxxterms.licenseref.startdate2018en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfTher Adv Med Oncolen_US
pubs.notesNot knownen_US
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine (de Bono Prostate)
pubs.publication-statusPublished onlineen_US
pubs.volume10en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicine (de Bono Prostate)en_US
dc.contributor.icrauthorLopez, Juanitaen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/