title: Evolving concepts in cancer therapy through targeting sphingolipid metabolism.
abstract: Traditional methods of cancer treatment are limited in their efficacy due to both inherent and acquired factors. Many different studies have shown that the generation of ceramide in response to cytotoxic therapy is generally an important step leading to cell death. Cancer cells employ different methods to both limit ceramide generation and to remove ceramide in order to become resistant to treatment. Furthermore, sphingosine kinase activity, which phosphorylates sphingosine the product of ceramide hydrolysis, has been linked to multidrug resistance, and can act as a strong survival factor. This review will examine several of the most frequently used cancer therapies and their effect on both ceramide generation and the mechanisms employed to remove it. The development and use of inhibitors of sphingosine kinase will be focused upon as an example of how targeting sphingolipid metabolism may provide an effective means to improve treatment response rates and reduce associated treatment toxicity. This article is part of a Special Issue entitled Tools to study lipid functions.
authors.affiliation: Health Science Center, Stony Brook University, 100 Nicolls Road, T15, 023, 11794 Stony Brook, NY, USA. Electronic address: Jean-Philip.Truman@stonybrookmedicine.edu.
authors.forename: Jean-Philip
authors.initials: JP
authors.lastname: Truman
authors.affiliation: Health Science Center, Stony Brook University, 100 Nicolls Road, T15, 023, 11794 Stony Brook, NY, USA. Electronic address: Monica.Garcia-Barros@stonybrookmedicine.edu.
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Barros
authors.affiliation: Northport Veterans Affairs Medical Center, Northport, NY 11768, USA; Health Science Center, Stony Brook University, 100 Nicolls Road, L4, 178, 11794 Stony Brook, NY, USA. Electronic address: Lina.Obeid@stonybrookmedicine.edu.
authors.forename: Lina M
authors.initials: LM
authors.lastname: Obeid
authors.affiliation: Department of Medicine and the Stony Brook Cancer Center, Health Science Center, Stony Brook University, 100 Nicolls Road, L4, 178, 11794 Stony Brook, NY, USA. Electronic address: Yusuf.Hannun@stonybrookmedicine.edu.
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D013107:Sphingolipids
keywords: Cancer; Ceramide; Chemoresistance; Inhibitor; Sphingosine kinase; Sphingosine-1-phosphate