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Targeting the ATR-CHK1 Axis in Cancer Therapy

Lookup NU author(s): Dr Stuart Rundle, Alice Bradbury, Dr Yvette DrewORCiD, Professor Nicola CurtinORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. 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.

Publication metadata

Author(s): Rundle S, Bradbury A, Drew Y, Curtin NJ

Publication type: Review

Publication status: Published

Journal: Cancers

Year: 2017

Volume: 9

Issue: 5

Online publication date: 27/04/2017

Acceptance date: 25/04/2017

ISSN (print): 2072-6694

Publisher: MDPI AG

URL: https://doi.org/10.3390/cancers9050041

DOI: 10.3390/cancers9050041

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