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dc.contributor.authorPettitt, SJen_US
dc.contributor.authorLord, CJen_US
dc.date.accessioned2019-06-04T10:08:34Z
dc.date.issued2019-02
dc.identifier.citationCurrent opinion in genetics & development, 2019, 54 pp. 55 - 63
dc.identifier.issn0959-437X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3250
dc.identifier.eissn1879-0380
dc.identifier.doi10.1016/j.gde.2019.03.001
dc.description.abstractThe poly-(ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib was the first licenced cancer drug that targeted an inherited form of cancer, namely ovarian cancers caused by germline BRCA1 or BRCA2 gene mutations. Multiple different PARPi have now been approved for use in a wider group of gynaecological cancers as well as for the treatment of BRCA-gene mutant breast cancer. Despite these advances, resistance to PARPi is a common clinical phenotype. Understanding, at the molecular level, how tumour cells respond to PARPi has the potential to inform how these drugs should be used clinically and since the discovery of this drug class, multiple different functional genomic strategies have been employed to dissect PARPi sensitivity and resistance. These have included genetic perturbation via classical gene targeting, gene silencing by siRNA or shRNA or transposon mutagenesis techniques. Recently, CRISPR-Cas9-based mutagenesis has greatly expanded the available range of relevant preclinical models and the precision of mutagenesis. Here, we review how these approaches have been used either in low-throughput, hypothesis-testing experiments or in the setting of large, hypothesis-generating, genetic screens aimed at understanding the molecular basis of PARPi sensitivity and resistance.
dc.formatPrint-Electronic
dc.format.extent55 - 63
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectOvarian Neoplasms
dc.subjectPiperazines
dc.subjectPhthalazines
dc.subjectPoly(ADP-ribose) Polymerases
dc.subjectBRCA1 Protein
dc.subjectBRCA2 Protein
dc.subjectDrug Resistance, Neoplasm
dc.subjectGerm-Line Mutation
dc.subjectFemale
dc.subjectPoly(ADP-ribose) Polymerase Inhibitors
dc.titleDissecting PARP inhibitor resistance with functional genomics.
dc.typeJournal Article
dcterms.dateAccepted2019-03-02
rioxxterms.versionofrecord10.1016/j.gde.2019.03.001
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2019-02
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCurrent opinion in genetics & development
pubs.notes12 months
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.volume54
pubs.embargo.terms12 months
icr.researchteamGene Functionen_US
dc.contributor.icrauthorLord, Christopheren
dc.contributor.icrauthorPettitt, Stephenen


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