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Novel Chemotherapeutic Drugs in Sphingolipid Cancer Research

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Sphingolipids: Basic Science and Drug Development

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 215))

Abstract

Sphingolipid-metabolizing enzymes are becoming targets for chemotherapeutic development with an increasing interest in the recent years. In this chapter we introduce the sphingolipid family of lipids, and the role of individual species in cell homeostasis. We also discuss their roles in several rare diseases and overall, in cancer transformation. We follow the biosynthesis pathway of the sphingolipid tree, focusing on the enzymes in order to understand how using small molecule inhibitors makes it possible to modulate cancer progression. Finally, we describe the most used and historically significant inhibitors employed in cancer research, their relationships to sphingolipid metabolism, and some promising results found in this field.

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Abbreviations

D-e-MAPP:

(1S, 2R)-D-erythro-2-(N-Myristoylamino)-1-phenyl-1-propanol

CDase (aCDase nCDase, alkCDase):

Ceramidase (acid, neutral, and alkaline ceramidase)

CerS:

Ceramide synthase

DES:

Dihydroceramide desaturase

GSC:

Glucosylceramide synthase

DMS:

N, N-dimethylsphingosine

TMS:

N, N, N-Trimethylsphingosine

NOE:

N-oleoylethanolamine

PKC:

Protein kinase C

SPT:

Serine-palmitoyl transferase

SMase (aSMase nSMase):

Sphingomyelinase (acid, neutral sphingomyelinase)

SMS:

Sphingomyelin synthase

SPP:

Sphingosine 1-phosphate phosphatase

SK:

Sphingosine kinase

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Acknowledgements

We gratefully acknowledge Dr. Mike Airola and María Hernández-Corbacho for the careful reading of this manuscript. This work was supported by NIH grants CA87584 and CA97132.

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Authors and Affiliations

  1. Department of Medicine, University of Stony Brook, Stony Brook, New York, 11794, USA

    Daniel Canals

  2. Health Science Center, Stony Brook University, 100 Nicolls Road, L-4, 178, Stony Brook, NY, 11794, USA

    Yusuf A. Hannun

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Correspondence to Yusuf A. Hannun .

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  1. , Department of Molecular Biology, University of Duisburg-Essen, Hufelandstraße 55, Essen, 45122, Germany

    Erich Gulbins

  2. Division of Pulmonary, Allergy, Critical, Department of Medicine, Indiana University School of Medicine, W. Walnut Street 980, Indianapolis, 46202, Indiana, USA

    Irina Petrache

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Canals, D., Hannun, Y.A. (2013). Novel Chemotherapeutic Drugs in Sphingolipid Cancer Research. In: Gulbins, E., Petrache, I. (eds) Sphingolipids: Basic Science and Drug Development. Handbook of Experimental Pharmacology, vol 215. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1368-4_12

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