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Cancers 2017, 9(5), 41; doi:10.3390/cancers9050041

Targeting the ATR-CHK1 Axis in Cancer Therapy

1
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
2
Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead NE9 6SX, UK
3
Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK
*
Authors to whom correspondence should be addressed.
Academic Editor: Eddy S. Yang
Received: 15 February 2017 / Revised: 23 April 2017 / Accepted: 25 April 2017 / Published: 27 April 2017
(This article belongs to the Special Issue DNA Repair Pathways in Cancer)
View Full-Text   |   Download PDF [3036 KB, uploaded 27 April 2017]   |  

Abstract

Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer that shows great promise for tumour selectivity. Key components of the DDR are the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1 (CHK1) kinases. This review article describes the role of ATR and its major downstream target, CHK1, in the DDR and why cancer cells are particularly reliant on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and validation of this hypothesis by genetic manipulation. The recent development of specific inhibitors and preclinical data using these inhibitors not only as chemosensitisers and radiosensitisers but also as single agents to exploit specific pathologies of tumour cells is described. These potent and specific inhibitors have now entered clinical trial and early results are presented. View Full-Text
Keywords: ATR; CHK1; cell cycle; chemotherapy-sensitising-agents; DNA-damage; DNA-repair; protein-kinase-inhibitors; radiation-sensitising-agents ATR; CHK1; cell cycle; chemotherapy-sensitising-agents; DNA-damage; DNA-repair; protein-kinase-inhibitors; radiation-sensitising-agents
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Rundle, S.; Bradbury, A.; Drew, Y.; Curtin, N.J. Targeting the ATR-CHK1 Axis in Cancer Therapy. Cancers 2017, 9, 41.

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