dc.contributor.author | Lord, CJ | |
dc.contributor.author | Ashworth, A | |
dc.date.accessioned | 2017-04-03T09:50:16Z | |
dc.date.issued | 2017-03-17 | |
dc.identifier.citation | Science (New York, N.Y.), 2017, 355 (6330), pp. 1152 - 1158 | |
dc.identifier.issn | 0036-8075 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/543 | |
dc.identifier.eissn | 1095-9203 | |
dc.identifier.doi | 10.1126/science.aam7344 | |
dc.description.abstract | PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease. In addition, determining the optimal use of PARPi within drug combination approaches has been challenging. Nevertheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical approval provide interesting lessons for the development of other therapies. Here, we discuss current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness. | |
dc.format | Print-Electronic | |
dc.format.extent | 1152 - 1158 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Neoplasms | |
dc.subject | DNA Damage | |
dc.subject | Ubiquitin-Protein Ligases | |
dc.subject | BRCA2 Protein | |
dc.subject | Antineoplastic Agents | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Antineoplastic Protocols | |
dc.subject | DNA Repair | |
dc.subject | Germ-Line Mutation | |
dc.subject | Clinical Trials as Topic | |
dc.subject | Poly(ADP-ribose) Polymerase Inhibitors | |
dc.subject | Synthetic Lethal Mutations | |
dc.title | PARP inhibitors: Synthetic lethality in the clinic. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-02-17 | |
rioxxterms.versionofrecord | 10.1126/science.aam7344 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-03-16 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Science (New York, N.Y.) | |
pubs.issue | 6330 | |
pubs.notes | No embargo | |
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-status | Published | |
pubs.volume | 355 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Gene Function | |
dc.contributor.icrauthor | Lord, Christopher | |