Targeting the ATR-CHK1 Axis in Cancer Therapy

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2017 Apr 28

PMID 28448462

Citations 111

Authors

Stuart Rundle

Alice Bradbury

Yvette Drew

Nicola J Curtin

Affiliations

Soon will be listed here.

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.

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