Targeting fatty acid metabolism in cancer and endothelial cells

• Fatty acid oxidation is required for de novo synthesis of nucleotides in endothelial cell, thus functional angiogenesis.
• The importance of other aspects of endothelial fatty acid metabolism requires further detailed investigation.
• Cancer fatty acid metabolism is required for survival and growth and to overcome periods of metabolic stress.
• In cancer cells ATP and NADPH derived from fatty acid oxidation enable protection from ROS and energy maintenance.
• Fatty acid oxidation is a potential target for anti-angiogenic therapies in cancer.

Tumour angiogenesis has long been recognised as a target for anti-cancer therapy. The current approach of inhibiting the VEGF pathway has shown benefit in the clinic, though less than anticipated. We recently documented that glycolytic metabolism in endothelial cells (ECs) fuels angiogenesis, rendering it a possible target for inhibiting vascular growth in pathological conditions. More recently, we reported that the oxidation of fatty acids (FA) is irreplaceable for EC proliferation by providing carbons for de novo nucleotide synthesis. Furthermore, ECs are rather unique in this respect, creating novel therapeutic opportunities. Here, we review and compare the current understanding of FA utilisation in ECs and tumour cells (TCs).