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2017 ; 9
(5
): ä Nephropedia Template TP
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Targeting the ATR-CHK1 Axis in Cancer Therapy
#MMPMID28448462
Rundle S
; Bradbury A
; Drew Y
; Curtin NJ
Cancers (Basel)
2017[Apr]; 9
(5
): ä PMID28448462
show ga
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.