title: Targeting the ceramide system in cancer.
abstract: Sphingolipids, in particular ceramide, have been described as important components of cellular signalling pathways. Ceramide can be produced via multiple mechanisms including through the hydrolysis of sphingomyelin by acid and neutral sphingomyelinase or by a de novo synthesis pathway. Recent studies have identified sphingomyelinases and ceramide synthases as important targets for γ-irradiation and chemotherapeutic drugs. Likewise, common cancer treatment modalities, such as γ-irradiation and many chemotherapeutic agents, induce cell death via the generation of ceramide. This suggests that the manipulation of ceramide production and metabolism could offer promising means for the enhancement of anti-tumor therapies. The focus of this mini-review will be to discuss contemporary evidence suggesting that ceramide forming pathways and ceramide itself are important targets for the treatment of tumors and the development of novel tumor treatment strategies.
authors.affiliation: Dept. of Molecular Biology, University of Duisburg-Essen, Hufelandstrasse 55, 45 122 Essen, Germany.
authors.forename: Brian
authors.initials: B
authors.lastname: Henry
authors.forename: Christina
authors.initials: C
authors.lastname: Möller
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Dimanche-Boitrel
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.forename: Katrin Anne
authors.initials: KA
authors.lastname: Becker
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D016923:Cell Death; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; C112980:acid sphingomyelinase-1; D013108:Sphingomyelin Phosphodiesterase; C519633:SMPD2 protein, human