Regulation of Sphingosine Kinase in Hematological Malignancies and Other Cancers

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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Regulation of Sphingosine Kinase in Hematological Malignancies and Other Cancers

Anti-Cancer Agents in Medicinal Chemistry, 11(9): 799-809.

Author(s): Stuart M. Pitson, Jason A. Powell and Claudine S Bonder.

Affiliation: Human Immunology, Centre for Cancer Biology, SA Pathology, Adelaide SA 5000, Australia.


The sphingolipids ceramide, sphingosine and sphingosine 1-phosphate have emerged as important signaling molecules that regulate a number of important cellular processes. Sphingosine 1-phosphate enhances cell survival and proliferation, and also regulates angiogenesis, cell invasion, and differentiation via both its cell surface G protein-coupled receptors and recently identified intracellular effectors. In contrast, ceramide and sphingosine elicit growth arrest and apoptosis through direct modulation of a number of intracellular targets. The cellular balance of these sphingolipids contributes to the determination of cell fate, and it is now clear that disruption in this ‘sphingolipid rheostat’ contributes to the development, progression and chemotherapeutic resistance of both hematological malignancies and solid tumors. The sphingosine kinases are central regulators of this pathway since they not only increase sphingosine 1-phosphate and assist in reduction of ceramide and sphingosine, but are also regulated at multiple levels by external stimuli. Thus, targeting the regulation of the sphingosine kinases may be a viable therapeutic strategy for a diverse array of cancers. Here, we describe the current knowledge of sphingosine kinase regulation, effects of current and potential chemotherapeutic agents on this system, and discuss the implications of this for the treatment of hematological malignancies and other cancers.


Cancer, Ceramide, Chronic myeloid leukemia, Hematological malignacy, Sphingosine, Sphingosine 1-phosphate, Sphingosine kinase, PKC, CML cells, AML, BCR-ABL, GDNF.

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Article Details

Volume: 11
Issue Number: 9
First Page: 799
Last Page: 809
Page Count: 11
DOI: 10.2174/187152011797655078
Price: $58

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