Bubici, C and Papa, S orcid.org/0000-0002-8369-6538 (2014) JNK signalling in cancer: in need of new, smarter therapeutic targets. British Journal of Pharmacology, 171 (1). pp. 24-37. ISSN 0007-1188
Abstract
The JNKs are master protein kinases that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival and death. It is increasingly apparent that persistent activation of JNKs is involved in cancer development and progression. Therefore, JNKs represent attractive targets for therapeutic intervention with small molecule kinase inhibitors. However, evidence supportive of a tumour suppressor role for the JNK proteins has also been documented. Recent studies showed that the two major JNK proteins, JNK1 and JNK2, have distinct or even opposing functions in different types of cancer. As such, close consideration of which JNK proteins are beneficial targets and, more importantly, what effect small molecule inhibitors of JNKs have on physiological processes, are essential. A number of ATP-competitive and ATP-non-competitive JNK inhibitors have been developed, but have several limitations such as a lack of specificity and cellular toxicity. In this review, we summarize the accumulating evidence supporting a role for the JNK proteins in the pathogenesis of different solid and haematological malignancies, and discuss many challenges and scientific opportunities in the targeting of JNKs in cancer.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 The British Pharmacological Society. This is the peer reviewed version of the following article: Bubici, C. and Papa, S. (2014), JNK signalling in cancer: in need of new, smarter therapeutic targets. British Journal of Pharmacology, 171: 24–37; which has been published in final form at https://dx.doi.org/10.1111/bph.12432. This article may be used for non-commercial purposes in accordance with the Wiley Terms and Conditions for Self-Archiving. |
Keywords: | JNK1; JNK2; PARP14; survival; apoptosis; multiple myeloma; hepatocellular carcinoma; cancer targets |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Haematology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Jul 2016 13:53 |
Last Modified: | 17 Jan 2018 16:37 |
Published Version: | https://dx.doi.org/10.1111/bph.12432 |
Status: | Published |
Publisher: | Wiley: 12 months |
Identification Number: | 10.1111/bph.12432 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101273 |