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Pancreatic Cancer and Sphingolipids

  • Samy A. F. Morad
  • Myles C. CabotEmail author

Abstract

Sphingolipid metabolism is an area of cancer science that has recently risen to prominence in the laboratory and in the clinical arena. This is because ceramide, the aliphatic backbone of sphingolipids, can act as a powerful tumor censor; a favorable attribute. However, cancer cells are equipped to efficiently inactivate ceramide via various metabolic routes: glycosylation to form glucosylceramide, and hydrolysis, which generates sphingosine and then, through the action of sphingosine kinase, sphingosine 1-phosphate, a tumor cell mitogen. These actions severely blunt ceramide anticancer properties, thwarting potential utility in treatment, and pancreatic cancer, a drug resistant, severely aggressive malignancy, is no exception. In this chapter we will review pancreatic cancer epidemiology, classical treatment options, and progression, and survey sphingolipid metabolism in pancreatic cancer as it relates to the action and efficacy of anticancer drugs. The work will conclude with ideas on how targeting ceramide metabolism could reveal new vulnerabilities for countering growth of this intractable malignancy.

Keywords

Pancreatic cancer Ceramide Sphingolipids Ceramide metabolism Ceramidase Glucosylceramide Glucosylceramide synthase Sphingomyelin Sphingomyelinase C6-ceramide 

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina Diabetes and Obesity InstituteEast Carolina UniversityGreenvilleUSA
  2. 2.Department of Pharmacology, Faculty of Veterinary MedicineSouth Valley UniversityQenaEgypt

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