New Insights Into Targeting Membrane Lipids for Cancer Therapy.

Giulio Preta

doi:10.3389/fcell.2020.571237

Abstract

Modulation of membrane lipid composition and organization is currently developing as an effective therapeutic strategy against a wide range of diseases, including cancer. This field, known as membrane-lipid therapy, has risen from new discoveries on the complex organization of lipids and between lipids and proteins in the plasma membranes. Membrane microdomains present in the membrane of all eukaryotic cells, known as lipid rafts, have been recognized as an important concentrating platform for protein receptors involved in the regulation of intracellular signaling, apoptosis, redox balance and immune response. The difference in lipid composition between the cellular membranes of healthy cells and tumor cells allows for the development of novel therapies based on targeting membrane lipids in cancer cells to increase sensitivity to chemotherapeutic agents and consequently defeat multidrug resistance. In the current manuscript strategies based on influencing cholesterol/sphingolipids content will be presented together with innovative ones, more focused in changing biophysical properties of the membrane bilayer without affecting the composition of its constituents.

Highlights

Lipid-driven membrane organization is essential for the physiological functions of eukaryotic cells since it regulates a multitude of processes including intracellular signaling, redox balance and cell death (Muro et al, 2014; Santos and Preta, 2018)
The better understanding of membrane lipid composition and organization gained in the last years, together with the lipidic alterations reported in tumor membranes, provides a big opportunity for cancer prevention and treatment
Rafts proteins have an essential role in regulating lipid properties and a future field of study in membrane-lipid therapy (MLT) could be the investigation of how changes in the structural composition of raft proteins influence lipid microdomains organization

Summary

Introduction

Lipid-driven membrane organization is essential for the physiological functions of eukaryotic cells since it regulates a multitude of processes including intracellular signaling, redox balance and cell death (Muro et al, 2014; Santos and Preta, 2018). Cancer cells re-organize their plasma membranes to preserve proliferation, escape apoptosis and resist to anticancer drugs treatment (Bernardes and Fialho, 2018). Altered ceramide metabolism in cancer has been described as an effective drug resistance mechanism: tumors have low levels of ceramide by increasing SM synthesis or by preventing its degradation (Senchenkov et al, 2001; Lewis et al, 2018).

Results

Conclusion