Targeting the ATR-CHK1 Axis in Cancer Therapy

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 AT...

Full description

Saved in:
Bibliographic Details
Published in:Cancers 2017-04, Vol.9 (5), p.41
Main Authors: Rundle, Stuart, Bradbury, Alice, Drew, Yvette, Curtin, Nicola J
Format: Article
Language:English
Subjects:
Ataxia telangiectasia mutated protein
Cancer
Cancer therapies
CHK1 protein
DNA damage
Kinases
Review
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers9050041