Ferroptosis and FASN

Ferroptosis, a form of programmed cell death characterized by iron-dependent lipid peroxidation, is a promising avenue in cancer therapy. New research shows that disrupting cancer cells' lipid metabolism can enhance their susceptibility to ferroptosis. Orlistat, an FDA-approved anti-obesity drug known for inhibiting fatty acid synthase (FASN), plays a pivotal role in this context.

A study by Lian and colleagues demonstrated that restricting cancer cells' access to fats increases their sensitivity to ferroptosis. By inhibiting FASN, Orlistat effectively reduces lipid synthesis within cancer cells, thereby promoting ferroptosis. This mechanism was observed in lung cancer cells, where orlistat inhibited cell proliferation and induced ferroptosis-like cell death. 

Combining orlistat with ferroptosis inducers could be an effective strategy for cancer treatment. By simultaneously disrupting lipid metabolism and inducing ferroptosis, this approach could potentially overcome resistance mechanisms that cancer cells employ against conventional therapies.

References

Sokol, K. H., et al (2024) Lipid availability influences ferroptosis sensitivity in cancer cells by regulating polyunsaturated fatty acid trafficking. Cell Chemical Biology. doi.org/10.1016/j.chembiol.2024.09.008.

Zhou, W., Zhang, J., Yan, M. et al. Orlistat induces ferroptosis-like cell death of lung cancer cells. Front. Med. 15, 922–932 (2021). https://doi.org/10.1007/s11684-020-0804-7