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dc.contributor.authorMinchom, Aen_US
dc.contributor.authorAversa, Cen_US
dc.contributor.authorLopez, Jen_US
dc.date.accessioned2019-02-25T16:08:32Z
dc.date.issued2018-01
dc.identifier.citationTherapeutic advances in medical oncology, 2018, 10 pp. 1758835918786658 - ?
dc.identifier.issn1758-8340
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3085
dc.identifier.eissn1758-8359
dc.identifier.doi10.1177/1758835918786658
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.
dc.formatElectronic-eCollection
dc.format.extent1758835918786658 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleDancing with the DNA damage response: next-generation anti-cancer therapeutic strategies.
dc.typeJournal Article
dcterms.dateAccepted2018-06-08
rioxxterms.versionofrecord10.1177/1758835918786658
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/4.0
rioxxterms.licenseref.startdate2018-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfTherapeutic advances in medical oncology
pubs.notesNot known
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
pubs.volume10
pubs.embargo.termsNot known
icr.researchteamMedicine (de Bono Prostate)en_US
dc.contributor.icrauthorLopez, Juanitaen


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