Cysteine depletion induces pancreatic tumor ferroptosis in mice
Michael A. Badgley, Daniel M. Kremer, H. Carlo Maurer, Kathleen E. DelGiorno, Ho‐Joon Lee, Vinee Purohit, Irina R. Sagalovskiy, Alice Ma, Jonathan Kapilian, Christina E. M. Firl, Amanda R. Decker-Farrell, Steve A. Sastra, Carmine F. Palermo, Leonardo R. Andrade, Peter Sajjakulnukit, Li Zhang, Zachary P. Tolstyka, Tal Hirschhorn, Candice Lamb, Tong Liu, Wei Gu, E. Scott Seeley, Everett Stone, George Georgiou, Uri Manor, Alina C. Iuga, Geoffrey M. Wahl, Brent R. Stockwell, Costas A. Lyssiotis, Kenneth P. Olive
Abstract
Ferroptotic cell death and cancer Cell death can occur through different mechanisms, several of which are being explored as potential targets for cancer treatment. One form of cell death that has attracted recent interest is ferroptosis, which is triggered by high intracellular levels of lipid reactive oxygen species. Pancreatic cancer cells have high levels of reactive oxygen species but manage to avoid ferroptosis by importing extracellular cysteine. Studying mice bearing pancreatic tumors, Badgley et al. found that administration of a drug inhibiting cysteine import induced tumor-selective ferroptosis and inhibited tumor growth. Further work will be required to determine whether this therapeutic strategy will be effective in human pancreatic cancer, a tumor type for which new treatments are urgently needed. Science , this issue p. 85