An orally bioavailable Chk1 inhibitor, CCT244747, sensitizes bladder and head and neck cancer cell lines to radiation.
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Date
2017-03-01Author
Patel, R
Barker, HE
Kyula, J
McLaughlin, M
Dillon, MT
Schick, U
Hafsi, H
Thompson, A
Khoo, V
Harrington, K
Zaidi, S
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Radiosensitization
Bladder cancer
Head and neck cancer
Radiation
Chkl inhibition
Research team
Targeted Therapy
Language
eng
License start date
2017-03
Citation
RADIOTHERAPY AND ONCOLOGY, 2017, 122 (3), pp. 470 - 475
Publisher
ELSEVIER IRELAND LTD