Therapeutic targeting of lipid synthesis metabolism for selective elimination of cancer stem cells.

Abstract

Cancer stem cells (CSCs) are believed to have an essential role in tumor resistance and metastasis; however, no therapeutic strategy for the selective elimination of CSCs has been established. Recently, several studies have shown that the metabolic regulation for ATP synthesis and biological building block generation in CSCs are different from that in bulk cancer cells and rather similar to that in normal tissue stem cells. To take advantage of this difference for CSC elimination therapy, many studies have tested the effect of blocking these metabolism. Two specific processes for lipid biosynthesis, i.e., fatty acid unsaturation and cholesterol biosynthesis, have been shown to be very effective and selective for CSC targets. In this review, lipid metabolism specific to CSCs are summarized. In addition, how monounsaturated fatty acid and cholesterol synthesis may contribute to CSC maintenance are discussed. Specifically, the molecular mechanism required for lipid synthesis and essential for stem cell biology is highlighted. The limit and preview of the lipid metabolism targeting for CSCs are also discussed.