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Lipids and Membrane Microdomains: The Glycerolipid and Alkylphosphocholine Class of Cancer Chemotherapeutic Drugs

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Lipid Signaling in Human Diseases

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 259))

Abstract

Synthetic antitumor lipids are metabolically stable lysophosphatidylcholine derivatives, encompassing a class of non-mutagenic drugs that selectively target cancerous cells. In this chapter we review the literature as relates to the clinical efficacy of these antitumor lipid drugs and how our understanding of their mode of action has evolved alongside key advances in our knowledge of membrane structure, organization, and function. First, the history of the development of this class of drugs is described, providing a summary of clinical outcomes of key members including edelfosine, miltefosine, perifosine, erufosine, and erucylphosphocholine. A detailed description of the biophysical properties of these drugs and specific drug–lipid interactions which may contribute to the selectivity of the antitumor lipids for cancer cells follows. An updated model on the mode of action of these lipid drugs as membrane disorganizing agents is presented. Membrane domain organization as opposed to targeting specific proteins on membranes is discussed. By altering membranes, these antitumor lipids inhibit many survival pathways while activating pro-apoptotic signals leading to cell demise.

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  1. University of Calgary, Calgary, AB, Canada

    Vanina Zaremberg, Suriakarthiga Ganesan & Mark Mahadeo

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    Julian Gomez-Cambronero

  2. Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA

    Michael A. Frohman

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Zaremberg, V., Ganesan, S., Mahadeo, M. (2019). Lipids and Membrane Microdomains: The Glycerolipid and Alkylphosphocholine Class of Cancer Chemotherapeutic Drugs. In: Gomez-Cambronero, J., Frohman, M. (eds) Lipid Signaling in Human Diseases. Handbook of Experimental Pharmacology, vol 259. Springer, Cham. https://doi.org/10.1007/164_2019_222

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