Ferroptosis, Acyl Starvation, and Breast Cancer

To maintain their growth rate, cancer cells must secure a supply of fatty acids, which are necessary for building cell membranes and maintaining energy processes. This is one of the reasons why tissues with intensive fatty acid metabolism, such as the mammary gland, are more likely to develop tumors. One natural or induced defense process against cancer is ferroptosis, which interferes with normal fatty acid metabolism. This leads to the oxidation of polyunsaturated fatty acids, which causes a rear-rangement of the metabolism and damages cell membranes. As a consequence of this oxidation, there is a shortage of nor-mal polyunsaturated fatty acids, which disturbs the compli-cated metabolism of fatty acids. This imbalance in metabolism, resulting from the deficiency of properly structured fatty acids, is called, by these authors, "acyl starvation." When cancer cells are exposed to alternating hypoxia and reoxygenation, they of-ten develop resistance to neoadjuvant therapies. Blocking the stearoyl-CoA desaturase - fatty acid-binding protein 4 - fatty acid translocase axis appears to be a promising pathway in the treatment of breast cancer. On the one hand, the inhibition of desaturase leads to the formation of toxic phospholipid hy-droperoxides in ferroptosis, whereas on the other hand, the in-hibition of fatty acid-binding protein 4 and translocase leads to a reduced uptake of fatty acids and disruption of the cellular transport of fatty acids, resulting in intracellular acyl starvation. The disruption in the metabolism of fatty acids in cancer cells may augment the effectiveness of neoadjuvant therapy.