dc.contributor.author | Patel, R | |
dc.contributor.author | Barker, HE | |
dc.contributor.author | Kyula, J | |
dc.contributor.author | McLaughlin, M | |
dc.contributor.author | Dillon, MT | |
dc.contributor.author | Schick, U | |
dc.contributor.author | Hafsi, H | |
dc.contributor.author | Thompson, A | |
dc.contributor.author | Khoo, V | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Zaidi, S | |
dc.date.accessioned | 2017-05-23T16:41:40Z | |
dc.date.issued | 2017-03-01 | |
dc.identifier | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000397691500023&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4b848928d1c3e5c86d298abb68475f9 | |
dc.identifier.citation | RADIOTHERAPY AND ONCOLOGY, 2017, 122 (3), pp. 470 - 475 | |
dc.identifier.issn | 0167-8140 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/658 | |
dc.identifier.eissn | 1879-0887 | |
dc.identifier.doi | 10.1016/j.radonc.2016.12.026 | |
dc.description.abstract | PURPOSE: 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.format.extent | 470 - 475 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER IRELAND LTD | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Radiosensitization | |
dc.subject | Bladder cancer | |
dc.subject | Head and neck cancer | |
dc.subject | Radiation | |
dc.subject | Chkl inhibition | |
dc.title | An orally bioavailable Chk1 inhibitor, CCT244747, sensitizes bladder and head and neck cancer cell lines to radiation. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1016/j.radonc.2016.12.026 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | RADIOTHERAPY AND ONCOLOGY | |
pubs.issue | 3 | |
pubs.notes | Not 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 | |
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.publication-status | Published | |
pubs.volume | 122 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Targeted Therapy | |
dc.contributor.icrauthor | Patel, Radhika | |
dc.contributor.icrauthor | McLaughlin, Martin | |
dc.contributor.icrauthor | Dillon, Magnus | |
dc.contributor.icrauthor | Harrington, Kevin | |