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dc.contributor.authorPatel, R
dc.contributor.authorBarker, HE
dc.contributor.authorKyula, J
dc.contributor.authorMcLaughlin, M
dc.contributor.authorDillon, MT
dc.contributor.authorSchick, U
dc.contributor.authorHafsi, H
dc.contributor.authorThompson, A
dc.contributor.authorKhoo, V
dc.contributor.authorHarrington, K
dc.contributor.authorZaidi, S
dc.date.accessioned2017-01-06T11:22:39Z
dc.date.issued2017-03
dc.identifier.citationRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2017, 122 (3), pp. 470 - 475
dc.identifier.issn0167-8140
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/378
dc.identifier.eissn1879-0887en_US
dc.identifier.doi10.1016/j.radonc.2016.12.026en_US
dc.description.abstractPurpose Chk1 inhibition increases cell sensitivity to both chemotherapy and radiotherapy in several tumour types and is, therefore, a promising anti-cancer approach. Although several Chk1 inhibitors have been developed, their clinical progress has been hampered by low bioavailability and off-target toxicities.Materials and methods We characterized the radiosensitizing activity of CCT244747, the first orally bioavailable Chk1 inhibitor. We used a panel of bladder and head and neck cancer cell lines and monitored the effect of combining CCT244747 with radiation both in in vitro and in vivo models.Results CCT244747 sensitized cancer cell lines to radiation in vitro and resulted in a growth delay in cancer xenograft models associated with a survival benefit. Radiosensitization was elicited by abrogation of the radiation-induced G2 arrest and premature entry into mitosis.Conclusions CCT244747 is a potent and specific Chk1 inhibitor that can be administered orally. It radiosensitizes tumour cell lines and represents a new therapy for clinical application in combination with radiotherapy.
dc.formatPrint-Electronic
dc.format.extent470 - 475
dc.languageeng
dc.language.isoeng
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectHead and Neck Neoplasms
dc.subjectAminopyridines
dc.subjectPyrimidines
dc.subjectHistones
dc.subjectRadiation-Sensitizing Agents
dc.subjectAdministration, Oral
dc.subjectFemale
dc.subjectUrinary Bladder Neoplasms
dc.subjectG2 Phase Cell Cycle Checkpoints
dc.subjectCheckpoint Kinase 1
dc.titleAn orally bioavailable Chk1 inhibitor, CCT244747, sensitizes bladder and head and neck cancer cell lines to radiation.
dc.typeJournal Article
dcterms.dateAccepted2016-12-22
rioxxterms.versionofrecord10.1016/j.radonc.2016.12.026
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2017-03en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
pubs.issue3
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/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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 Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume122en_US
pubs.embargo.termsNot known
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorPatel, Radhikaen
dc.contributor.icrauthorMcLaughlin, Martinen
dc.contributor.icrauthorDillon, Magnusen
dc.contributor.icrauthorHarrington, Kevinen
dc.contributor.icrauthorZaidi, Shane Haideren
dc.contributor.icrauthorMarsden,en


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