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dc.contributor.authorAshworth, A
dc.contributor.authorLord, CJ
dc.date.accessioned2018-08-08T13:14:37Z
dc.date.issued2018-09
dc.identifier.citationNature reviews. Clinical oncology, 2018, 15 (9), pp. 564 - 576
dc.identifier.issn1759-4774
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2306
dc.identifier.eissn1759-4782
dc.identifier.doi10.1038/s41571-018-0055-6
dc.description.abstractThe genetic concept of synthetic lethality has now been validated clinically through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of cancers in individuals with germline loss-of-function mutations in either BRCA1 or BRCA2. Three different PARP inhibitors have now been approved for the treatment of patients with BRCA-mutant ovarian cancer and one for those with BRCA-mutant breast cancer; these agents have also shown promising results in patients with BRCA-mutant prostate cancer. Here, we describe a number of other synthetic lethal interactions that have been discovered in cancer. We discuss some of the underlying principles that might increase the likelihood of clinical efficacy and how new computational and experimental approaches are now facilitating the discovery and validation of synthetic lethal interactions. Finally, we make suggestions on possible future directions and challenges facing researchers in this field.
dc.formatPrint
dc.format.extent564 - 576
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectOvarian Neoplasms
dc.subjectPoly(ADP-ribose) Polymerases
dc.subjectBRCA1 Protein
dc.subjectBRCA2 Protein
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.subjectPoly(ADP-ribose) Polymerase Inhibitors
dc.subjectSynthetic Lethal Mutations
dc.subjectLoss of Function Mutation
dc.titleSynthetic lethal therapies for cancer: what's next after PARP inhibitors?
dc.typeJournal Article
dcterms.dateAccepted2018-05-31
rioxxterms.versionofrecord10.1038/s41571-018-0055-6
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature reviews. Clinical oncology
pubs.issue9
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.publication-statusPublished
pubs.volume15
pubs.embargo.termsNot known
icr.researchteamGene Functionen_US
dc.contributor.icrauthorLord, Christopheren


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