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dc.contributor.authorMateo, J
dc.contributor.authorLord, CJ
dc.contributor.authorSerra, V
dc.contributor.authorTutt, A
dc.contributor.authorBalmaña, J
dc.contributor.authorCastroviejo-Bermejo, M
dc.contributor.authorCruz, C
dc.contributor.authorOaknin, A
dc.contributor.authorKaye, SB
dc.contributor.authorde Bono, JS
dc.date.accessioned2019-09-16T15:07:44Z
dc.date.issued2019-09
dc.identifier.citationAnnals of oncology : official journal of the European Society for Medical Oncology, 2019, 30 (9), pp. 1437 - 1447
dc.identifier.issn0923-7534
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3334
dc.identifier.eissn1569-8041
dc.identifier.doi10.1093/annonc/mdz192
dc.description.abstractGenomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce tumour-specific vulnerabilities that can be exploited therapeutically. In 2009, a first-in-man clinical trial of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib clinically validated the synthetic lethal interaction between inhibition of PARP1, a key sensor of DNA damage, and BRCA1/BRCA2 deficiency. In this review, we summarize a decade of PARP inhibitor clinical development, a work that has resulted in the registration of several PARP inhibitors in breast (olaparib and talazoparib) and ovarian cancer (olaparib, niraparib and rucaparib, either alone or following platinum chemotherapy as maintenance therapy). Over the past 10 years, our knowledge on the mechanism of action of PARP inhibitor as well as how tumours become resistant has been extended, and we summarise this work here. We also discuss opportunities for expanding the precision medicine approach with PARP inhibitors, identifying a wider population who could benefit from this drug class. This includes developing and validating better predictive biomarkers for patient stratification, mainly based on homologous recombination defects beyond BRCA1/BRCA2 mutations, identifying DNA repair deficient tumours in other cancer types such as prostate or pancreatic cancer, or by designing combination therapies with PARP inhibitors.
dc.formatPrint
dc.format.extent1437 - 1447
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectOvarian Neoplasms
dc.subjectGenomic Instability
dc.subjectPiperazines
dc.subjectPiperidines
dc.subjectIndazoles
dc.subjectPhthalazines
dc.subjectIndoles
dc.subjectBRCA1 Protein
dc.subjectBRCA2 Protein
dc.subjectFemale
dc.subjectPoly(ADP-ribose) Polymerase Inhibitors
dc.subjectPoly (ADP-Ribose) Polymerase-1
dc.titleA decade of clinical development of PARP inhibitors in perspective.
dc.typeJournal Article
rioxxterms.versionofrecord10.1093/annonc/mdz192
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/4.0
rioxxterms.licenseref.startdate2019-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAnnals of oncology : official journal of the European Society for Medical 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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine Drug Development Unit (Kaye)
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine Drug Development Unit (Kaye)
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.volume30
pubs.embargo.termsNot known
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamMedicine Drug Development Unit (Kaye)en_US
icr.researchteamGene Functionen_US
dc.contributor.icrauthorKaye, Stanley Bernarden
dc.contributor.icrauthorLord, Christopheren
dc.contributor.icrauthorDe Bono, Johannen
dc.contributor.icrauthorTutt, Andrewen


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