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Pharmacological targeting of IRE1 in cancer

Abstract:
IRE1α (inositol requiring enzyme 1 alpha) is one of the main transducers of the unfolded protein response (UPR). IRE1α plays instrumental protumoral roles in several cancers, and high IRE1α activity has been associated with poorer prognoses. In this context, IRE1α has been identified as a potentially relevant therapeutic target. Pharmacological inhibition of IRE1α activity can be achieved by targeting either the kinase domain or the RNase domain. Herein, the recent advances in IRE1α pharmacological targeting is summarized. We describe the identification and optimization of IRE1α inhibitors as well as their mode of action and limitations as anticancer drugs. The potential pitfalls and challenges that could be faced in the clinic, and the opportunities that IRE1α modulating strategies may present are discussed.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.trecan.2020.07.006

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
Surgical Sciences
Role:
Author


Publisher:
Cell Press
Journal:
Trends in Cancer More from this journal
Volume:
6
Issue:
12
Pages:
1018-1030
Publication date:
2020-08-26
DOI:
EISSN:
2405-8033


Language:
English
Keywords:
Pubs id:
1129765
Local pid:
pubs:1129765
Deposit date:
2020-09-02
ARK identifier:

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