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dc.contributor.authorWhittaker, SR
dc.contributor.authorMallinger, A
dc.contributor.authorWorkman, P
dc.contributor.authorClarke, PA
dc.date.accessioned2017-11-06T12:09:34Z
dc.date.issued2017-05-01
dc.identifier.citationPharmacology & therapeutics, 2017, 173 pp. 83 - 105
dc.identifier.issn0163-7258
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/900
dc.identifier.eissn1879-016X
dc.identifier.doi10.1016/j.pharmthera.2017.02.008
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.
dc.formatPrint-Electronic
dc.format.extent83 - 105
dc.languageeng
dc.language.isoeng
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectAnimals
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectCyclin-Dependent Kinases
dc.subjectAntineoplastic Agents
dc.subjectProtein Kinase Inhibitors
dc.subjectCell Cycle
dc.subjectCell Proliferation
dc.subjectDrug Design
dc.subjectMolecular Targeted Therapy
dc.titleInhibitors of cyclin-dependent kinases as cancer therapeutics.
dc.typeJournal Article
dcterms.dateAccepted2017-02-05
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1016/j.pharmthera.2017.02.008
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2017-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPharmacology & therapeutics
pubs.notesNo 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/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.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-statusPublished
pubs.volume173
pubs.embargo.termsNo embargo
icr.researchteamMolecular Drug Resistance
icr.researchteamSignal Transduction & Molecular Pharmacology
dc.contributor.icrauthorWhittaker, Steven
dc.contributor.icrauthorWorkman, Paul
dc.contributor.icrauthorClarke, Paul


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