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dc.contributor.authorWhittaker, SRen_US
dc.contributor.authorMallinger, Aen_US
dc.contributor.authorWorkman, Pen_US
dc.contributor.authorClarke, PAen_US
dc.date.accessioned2017-11-06T12:09:34Z
dc.date.issued2017-05en_US
dc.identifier.citationPharmacology & therapeutics, 2017, 173 pp. 83 - 105en_US
dc.identifier.issn0163-7258en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/900
dc.identifier.eissn1879-016Xen_US
dc.identifier.doi10.1016/j.pharmthera.2017.02.008en_US
dc.description.abstractOver the past two decades there has been a great deal of interest in the development of inhibitors of the cyclin-dependent kinases (CDKs). This attention initially stemmed from observations that different CDK isoforms have key roles in cancer cell proliferation through loss of regulation of the cell cycle, a hallmark feature of cancer. CDKs have now been shown to regulate other processes, particularly various aspects of transcription. The early non-selective CDK inhibitors exhibited considerable toxicity and proved to be insufficiently active in most cancers. The lack of patient selection biomarkers and an absence of understanding of the inhibitory profile required for efficacy hampered the development of these inhibitors. However, the advent of potent isoform-selective inhibitors with accompanying biomarkers has re-ignited interest. Palbociclib, a selective CDK4/6 inhibitor, is now approved for the treatment of ER+/HER2- advanced breast cancer. Current developments in the field include the identification of potent and selective inhibitors of the transcriptional CDKs; these include tool compounds that have allowed exploration of individual CDKs as cancer targets and the determination of their potential therapeutic windows. Biomarkers that allow the selection of patients likely to respond are now being discovered. Drug resistance has emerged as a major hurdle in the clinic for most protein kinase inhibitors and resistance mechanism are beginning to be identified for CDK inhibitors. This suggests that the selective inhibitors may be best used combined with standard of care or other molecularly targeted agents now in development rather than in isolation as monotherapies.en_US
dc.formatPrint-Electronicen_US
dc.format.extent83 - 105en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.subjectAnimalsen_US
dc.subjectHumansen_US
dc.subjectNeoplasmsen_US
dc.subjectCyclin-Dependent Kinasesen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectProtein Kinase Inhibitorsen_US
dc.subjectCell Cycleen_US
dc.subjectCell Proliferationen_US
dc.subjectDrug Designen_US
dc.subjectMolecular Targeted Therapyen_US
dc.titleInhibitors of cyclin-dependent kinases as cancer therapeutics.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-02-05en_US
rioxxterms.funderThe Institute of Cancer Researchen_US
rioxxterms.identifier.projectUnspecifieden_US
rioxxterms.versionofrecord10.1016/j.pharmthera.2017.02.008en_US
rioxxterms.licenseref.urien_US
rioxxterms.licenseref.startdate2017-05en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfPharmacology & therapeuticsen_US
pubs.notesNo embargoen_US
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Molecular Drug Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.publication-statusPublisheden_US
pubs.volume173en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamMolecular Drug Resistanceen_US
icr.researchteamSignal Transduction & Molecular Pharmacologyen_US
dc.contributor.icrauthorWhittaker, Stevenen_US
dc.contributor.icrauthorClarke, Paulen_US
dc.contributor.icrauthorWorkman, Paulen_US
rioxxterms.funder.project354849bd-c553-4e22-868c-8c503e124155en_US


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