title: Sphingolipids and response to chemotherapy.
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.
authors.affiliation: Université de Rennes 1, Institut de Recherche Santé Environnement et Travail, Rennes, France. marie-therese.boitrel@univ-rennes1.fr
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Dimanche-Boitrel
authors.forename: Amélie
authors.initials: A
authors.lastname: Rebillard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D055572:Ceramidases / Q000378:metabolism; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D005964:Glucosyltransferases / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010088:Oxidoreductases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D000970:Antineoplastic Agents; D055572:Ceramidases; D005964:Glucosyltransferases; D010088:Oxidoreductases; D017853:Phosphotransferases (Alcohol Group Acceptor); D047428:Protein Kinase Inhibitors; D013107:Sphingolipids; D013108:Sphingomyelin Phosphodiesterase; D000099157:Sphingosine Kinase; C108138:dihydroceramide desaturase; C023246:ceramide glucosyltransferase; C066324:ceramide kinase