dc.contributor.author | Pettitt, SJ | |
dc.contributor.author | Lord, CJ | |
dc.date.accessioned | 2019-06-04T10:08:34Z | |
dc.date.issued | 2019-02-01 | |
dc.identifier.citation | Current opinion in genetics & development, 2019, 54 pp. 55 - 63 | |
dc.identifier.issn | 0959-437X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3250 | |
dc.identifier.eissn | 1879-0380 | |
dc.identifier.doi | 10.1016/j.gde.2019.03.001 | |
dc.description.abstract | The 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.format | Print-Electronic | |
dc.format.extent | 55 - 63 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CURRENT BIOLOGY LTD | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Ovarian Neoplasms | |
dc.subject | Piperazines | |
dc.subject | Phthalazines | |
dc.subject | Poly(ADP-ribose) Polymerases | |
dc.subject | BRCA1 Protein | |
dc.subject | BRCA2 Protein | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Germ-Line Mutation | |
dc.subject | Female | |
dc.subject | Poly(ADP-ribose) Polymerase Inhibitors | |
dc.title | Dissecting PARP inhibitor resistance with functional genomics. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-03-02 | |
rioxxterms.versionofrecord | 10.1016/j.gde.2019.03.001 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2019-02 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Current opinion in genetics & development | |
pubs.notes | 12 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-status | Published | |
pubs.volume | 54 | |
pubs.embargo.terms | 12 months | |
icr.researchteam | Gene Function | |
dc.contributor.icrauthor | Pettitt, Stephen | |
dc.contributor.icrauthor | Lord, Christopher | |