Targeting ceramide metabolism--a strategy for overcoming drug resistance.
Inherent or acquired drug resistance, which frequently characterizes cancer cells, is caused by multiple mechanisms, including dysfunctional metabolism of the lipid second messenger ceramide. Ceramide, the basic structural unit of the sphingolipids, plays a role in activating cell death signals initiated by cytokines, chemotherapeutic agents, and ionizing radiation. Recent discoveries about the metabolism of ceramide suggest that this agent may have an important influence on the effectiveness of various cancer therapeutics. In particular, the cytotoxic effect of chemotherapy is decreased when generation of ceramide is impaired but is increased when the degradation of ceramide is blocked. Herein, we review the mechanisms of resistance to chemotherapeutic agents in terms of ceramide metabolism.
Breast Cancer Research Program and Chemotherapeutics, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.
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Senchenkov
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Litvak
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MC
Cabot
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005963:Glucosylceramides / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000532:radiotherapy; D015398:Signal Transduction / Q000187:drug effects; D013109:Sphingomyelins / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000970:Antineoplastic Agents; D002518:Ceramides; D005963:Glucosylceramides; D013109:Sphingomyelins; D013110:Sphingosine; C005682:safingol