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Updated: Jul 19, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Glycosphingolipids and drug resistance
Valerie Gouaze-Andersson1, Myles C Cabot
1Department of Experimental Therapeutics, The John Wayne Cancer Institute at Saint John's Health Center, 2200 Santa Monica Blvd., Santa Monica, CA 90404, USA.
Abstract:
Drug resistance, an all too frequent characteristic of cancer, represents a serious barrier to successful treatment. Although many resistance mechanisms have been described, those that involve membrane-resident proteins belonging to the ABC (ATP binding cassette) transporter superfamily are of particular interest. In addition to cancer, the ABC transporter proteins are active in diseases such as malaria and leishmaniasis. A recent renaissance in lipid metabolism, specifically ceramide and sphingolipids, has fueled research and provided insight into the role of glycosphingolipids in multidrug resistance. This article reviews current knowledge on ceramide, glucosylceramide synthase and cerebrosides, and the relationship of these lipids to cellular response to anticancer agents.
Insights
Drug resistance in cancer is a major challenge. This review explores how ATP binding cassette (ABC) transporters and lipid metabolism, particularly ceramide and sphingolipids, influence multidrug resistance and cellular response to anticancer agents.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Drug resistance is a significant obstacle in cancer therapy.
- ATP binding cassette (ABC) transporters are key membrane proteins implicated in multidrug resistance.
- ABC transporters also play roles in other diseases like malaria and leishmaniasis.
Purpose of the Study:
- To review current understanding of ceramide, glucosylceramide synthase, and cerebrosides.
- To elucidate the relationship between these lipids and cellular response to anticancer drugs.
- To highlight the role of lipid metabolism in overcoming multidrug resistance.
Main Methods:
- Literature review of current research on lipid metabolism and drug resistance.
- Analysis of studies focusing on ceramide, glucosylceramide synthase, and cerebrosides.
- Integration of findings on ABC transporters and their link to glycosphingolipids.
Main Results:
- Glycosphingolipids, including ceramide and its derivatives, are increasingly recognized for their role in multidrug resistance.
- Specific enzymes like glucosylceramide synthase are critical in modulating cellular lipid profiles and drug sensitivity.
- Altering lipid metabolism pathways may offer novel strategies to combat cancer drug resistance.
Conclusions:
- Lipid metabolism, particularly involving ceramide and sphingolipids, is intricately linked to cancer multidrug resistance.
- Targeting lipid synthesis pathways presents a promising avenue for developing new anticancer therapies.
- Further research into the precise mechanisms of glycosphingolipids in ABC transporter function is warranted.
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