Chapter Six – Therapeutic Potential of Targeting SK1 in Human Cancers

Alshaker, Heba, Sauer, Lysann, Monteil, Danielle, Ottaviani, Silvia, Srivats, Shyam, Böhler, Torsten and Pchejetski, Dmitri (2013) Chapter Six – Therapeutic Potential of Targeting SK1 in Human Cancers. In: Advances in Cancer Research. Advances in Cancer Research, 117 . Elsevier, pp. 143-200. ISBN 978-0-12-394274-6

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Abstract

Sphingosine kinase 1 (SK1) is a lipid enzyme with oncogenic properties that converts the proapoptotic lipids ceramide and sphingosine into the antiapoptotic lipid sphingosine-1-phosphate and activates the signal transduction pathways that lead to cell proliferation, migration, the activation of the inflammatory response, and the impairment of apoptosis. There is compelling evidence that SK1 activation contributes to cancer progression leading to increased oncogenic transformation, tumor growth, resistance to therapies, tumor neovascularization, and metastatic spread. High levels of SK1 expression or activity have been associated with a poor prognosis in several human cancers. Recent studies using cancer cell and mouse models demonstrate a significant potential for SK1-targeting therapies to synergize with the effects of chemotherapy and radiotherapy; however, until recently the absence of clinically applicable SK1 inhibitors has limited the translation of these findings into patients. With the recent discovery of SK1 inhibiting properties of a clinically approved drug FTY720 (Fingolimod), SK1 has gained significant attention from both clinicians and the pharmaceutical industry and it is hoped that trials of newly developed SK1 inhibitors may follow soon. This review provides an overview of the SK1 signaling, its relevance to cancer progression, and the potential clinical significance of targeting SK1 for improved local or systemic control of human cancers.

Item Type: Book Section
Additional Information: Copyright © 2013 Elsevier Inc. All rights reserved.
Uncontrolled Keywords: animals,antineoplastic agents,humans,lysophospholipids,mice,neoplasms,phosphotransferases (alcohol group acceptor),signal transduction,sphingosine
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 16 Dec 2014 10:04
Last Modified: 25 Jul 2019 04:21
URI: https://ueaeprints.uea.ac.uk/id/eprint/51527
DOI: 10.1016/B978-0-12-394274-6.00006-6

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