Cysteine depletion induces pancreatic tumor ferroptosis in mice

Michael A. Badgley(Columbia University Irving Medical Center), Daniel M. Kremer(University of Michigan), H. Carlo Maurer(Columbia University Irving Medical Center), Kathleen E. DelGiorno(Salk Institute for Biological Studies), Ho‐Joon Lee(University of Michigan), Vinee Purohit(University of Michigan), Irina R. Sagalovskiy(Columbia University Irving Medical Center), Alice Ma(Columbia University Irving Medical Center), Jonathan Kapilian(Columbia University Irving Medical Center), Christina E. M. Firl(Columbia University Irving Medical Center), Amanda R. Decker-Farrell(Columbia University Irving Medical Center), Steve A. Sastra(Columbia University Irving Medical Center), Carmine F. Palermo(Columbia University Irving Medical Center), Leonardo R. Andrade(Salk Institute for Biological Studies), Peter Sajjakulnukit(University of Michigan), Li Zhang(University of Michigan), Zachary P. Tolstyka(University of Michigan), Tal Hirschhorn(Columbia University), Candice Lamb(The University of Texas at Austin), Tong Liu(Columbia University Irving Medical Center), Wei Gu(Columbia University Irving Medical Center), E. Scott Seeley(University of California, San Francisco), Everett Stone(The University of Texas at Austin), George Georgiou(The University of Texas at Austin), Uri Manor(Salk Institute for Biological Studies), Alina C. Iuga(Columbia University Irving Medical Center), Geoffrey M. Wahl(Salk Institute for Biological Studies), Brent R. Stockwell(Columbia University), Costas A. Lyssiotis(University of Michigan), Kenneth P. Olive(Columbia University Irving Medical Center)
Science
April 2, 2020
Cited by 1,238Open Access
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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


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