Cysteine depletion induces pancreatic tumor ferroptosis in mice
Michael A. BadgleyDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USADaniel M. KremerDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USAH. Carlo MaurerDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USAKathleen E. DelGiornoGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USAHo‐Joon LeeDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USAVinee PurohitDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USAIrina R. SagalovskiyDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USAAlice MaDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USAJonathan KapilianDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USAChristina E. M. FirlDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USAAmanda R. Decker-FarrellDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USASteve A. SastraDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USACarmine F. PalermoDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USALeonardo R. AndradeWaitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037, USAPeter SajjakulnukitDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USALi ZhangMichigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, MI 48105, USAZachary P. TolstykaDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USATal HirschhornDepartments of Biological Sciences and Chemistry, Columbia University, New York, NY 10027, USACandice LambDepartment of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USATong LiuDepartment of Pathology, Columbia University Medical Center, New York, NY 10032, USAWei GuDepartment of Pathology, Columbia University Medical Center, New York, NY 10032, USAE. Scott SeeleySalvo Therapeutics, San Francisco, CA 94117, USAEverett StoneDepartment of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USAGeorge GeorgiouDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USAUri ManorWaitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037, USAAlina C. IugaDepartment of Pathology, Columbia University Medical Center, New York, NY 10032, USAGeoffrey M. WahlGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USABrent R. StockwellDepartments of Biological Sciences and Chemistry, Columbia University, New York, NY 10027, USACostas A. LyssiotisDepartment of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USAKenneth P. OliveDivision of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
2020en
ABI
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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