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dc.contributor.authorBrown, JS
dc.contributor.authorO'Carrigan, B
dc.contributor.authorJackson, SP
dc.contributor.authorYap, TA
dc.date.accessioned2017-03-30T11:34:22Z
dc.date.issued2017-01
dc.identifier.citationCancer discovery, 2017, 7 (1), pp. 20 - 37
dc.identifier.issn2159-8274
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/536
dc.identifier.eissn2159-8290
dc.identifier.doi10.1158/2159-8290.cd-16-0860
dc.description.abstractGermline aberrations in critical DNA-repair and DNA damage-response (DDR) genes cause cancer predisposition, whereas various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2-mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell-cycle checkpoint activation, trigger apoptosis, and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations.Significance Various inhibitors of DDR components are in preclinical and clinical development. A thorough understanding of DDR pathway complexities must now be combined with strategies and lessons learned from the successful registration of PARP inhibitors in order to fully exploit the potential of DDR inhibitors and to ensure their long-term clinical success. Cancer Discov; 7(1); 20-37. ©2016 AACR.
dc.formatPrint-Electronic
dc.format.extent20 - 37
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectAnimals
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectAntineoplastic Agents
dc.subjectDrug Screening Assays, Antitumor
dc.subjectDNA Repair
dc.subjectMutation
dc.subjectPoly(ADP-ribose) Polymerase Inhibitors
dc.titleTargeting DNA Repair in Cancer: Beyond PARP Inhibitors.
dc.typeJournal Article
dcterms.dateAccepted2016-11-07
rioxxterms.versionofrecord10.1158/2159-8290.cd-16-0860
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer discovery
pubs.issue1
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 Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono)
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume7
pubs.embargo.termsNot known
icr.researchteamMedicine Drug Development Unit (de Bono)en_US
dc.contributor.icrauthorYap, Timothyen
dc.contributor.icrauthorMarsden,en


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