Abstract
The bioactive sphingolipid, ceramide, has garnered major interest as a principle regulator of cellular stress, proliferation, senescence, and death. Of particular interest to cancer biologists and clinical oncologist, dysregulated ceramide metabolism has been documented in both solid and non-solid malignancies. Moreover, most anticancer chemotherapeutics stimulate ceramide accumulation through increased ceramide synthesis or through the inhibition of ceramide catabolism. In fact, neutralization of ceramide via glycosylation or phosphorylation in malignant cells has been linked to multidrug chemoresistance. New therapeutic strategies to overcome chemoresistance focus on increasing endogenous ceramide levels by stimulating ceramide synthesis, by inhibiting ceramide neutralization, or by the direct delivery of exogenous ceramide. This review will discuss new therapeutic strategies designed specifically to modulate ceramide metabolism, as well as nanoscale delivery systems engineered to selectively deliver ceramide to cancerous cells and tissues.
Keywords: Ceramide, sphingolipids, nanotechnology, drug delivery, CERT, S1P, DMS, D-MAPP, LGL, CPSNP, PEG, PBMCs
Anti-Cancer Agents in Medicinal Chemistry
Title: Ceramide-Based Therapeutics for the Treatment of Cancer
Volume: 11 Issue: 9
Author(s): Brian M. Barth, Myles C. Cabot and Mark Kester
Affiliation:
Keywords: Ceramide, sphingolipids, nanotechnology, drug delivery, CERT, S1P, DMS, D-MAPP, LGL, CPSNP, PEG, PBMCs
Abstract: The bioactive sphingolipid, ceramide, has garnered major interest as a principle regulator of cellular stress, proliferation, senescence, and death. Of particular interest to cancer biologists and clinical oncologist, dysregulated ceramide metabolism has been documented in both solid and non-solid malignancies. Moreover, most anticancer chemotherapeutics stimulate ceramide accumulation through increased ceramide synthesis or through the inhibition of ceramide catabolism. In fact, neutralization of ceramide via glycosylation or phosphorylation in malignant cells has been linked to multidrug chemoresistance. New therapeutic strategies to overcome chemoresistance focus on increasing endogenous ceramide levels by stimulating ceramide synthesis, by inhibiting ceramide neutralization, or by the direct delivery of exogenous ceramide. This review will discuss new therapeutic strategies designed specifically to modulate ceramide metabolism, as well as nanoscale delivery systems engineered to selectively deliver ceramide to cancerous cells and tissues.
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Cite this article as:
M. Barth Brian, C. Cabot Myles and Kester Mark, Ceramide-Based Therapeutics for the Treatment of Cancer, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (9) . https://dx.doi.org/10.2174/187152011797655177
DOI https://dx.doi.org/10.2174/187152011797655177 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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