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Sphingolipids and Response to Chemotherapy

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Sphingolipids in Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 216))

Abstract

Chemotherapy is frequently used to treat primary or metastatic cancers, but intrinsic or acquired drug resistance limits its efficiency. Sphingolipids are important regulators of various cellular processes including proliferation, apoptosis, differentiation, angiogenesis, stress, and inflammatory responses which are linked to various aspects of cancer, like tumor growth, neoangiogenesis, and response to chemotherapy. Ceramide, the central molecule of sphingolipid metabolism, generally mediates antiproliferative and proapoptotic functions, whereas sphingosine-1-phosphate and other derivatives have opposing effects. Among the variety of enzymes that control ceramide generation, acid or neutral sphingomyelinases and ceramide synthases are important targets to allow killing of cancer cells by chemotherapeutic drugs. On the contrary, glucosylceramide synthase, ceramidase, and sphingosine kinase are other targets driving cancer cell resistance to chemotherapy. This chapter focuses on ceramide-based mechanisms leading to cancer therapy sensitization or resistance which could have some impacts on the development of novel cancer therapeutic strategies.

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Acknowledgements

Research in the IRSET INSERM U1085 group was supported by grants from the Ligue Nationale Contre le Cancer (the Côte d’Armor, Ille et Vilaine, Morbihan, Vendée, and Sarthe Comittees), INSERM, University of Rennes 1, and the Region Bretagne.

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  1. Université de Rennes 1, Institut de Recherche Santé Environnement et Travail (IRSET), 35043, Rennes, France

    Marie-Thérèse Dimanche-Boitrel

  2. Institut National de la Santé et de la Recherche Médicale (INSERM), U1085, Team “Stress, Membrane and Signaling”, 35043, Rennes, France

    Marie-Thérèse Dimanche-Boitrel

  3. EA 1274, Laboratoire “Mouvement, Sport, Santé”, University of Rennes 2, 35044, Rennes, France

    Amélie Rebillard

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  1. Marie-Thérèse Dimanche-Boitrel
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  2. Amélie Rebillard
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Correspondence to Marie-Thérèse Dimanche-Boitrel .

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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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Dimanche-Boitrel, MT., Rebillard, A. (2013). Sphingolipids and Response to Chemotherapy. In: Gulbins, E., Petrache, I. (eds) Sphingolipids in Disease. Handbook of Experimental Pharmacology, vol 216. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1511-4_4

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