Cited by 1,294Ferroptosis and cancer prognosisCell death mechanisms and regulationPancreatic and Hepatic Oncology Research

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Cysteine depletion induces pancreatic tumor ferroptosis in mice

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Badgley, Michael A., Kremer, Daniel M., Maurer, H. Carlo, DelGiorno, Kathleen E., Lee, Ho-Joon, Purohit, Vinee, Sagalovskiy, Irina R., Ma, Alice, Kapilian, Jonathan, Firl, Christina E. M., Decker, Amanda R., Sastra, Steve A., Palermo, Carmine F., Andrade, Leonardo R., Sajjakulnukit, Peter, Zhang, Li, Tolstyka, Zachary P., Hirschhorn, Tal, Lamb, Candice, Liu, Tong, Gu, Wei, Seeley, E. Scott, Stone, Everett, Georgiou, George, Manor, Uri, Iuga, Alina, Wahl, Geoffrey M., Stockwell, Brent R., Lyssiotis, Costas A., Olive, Kenneth P.·2020·Science

DOI 10.1126/science.aaw9872PMC PMC7681911

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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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Authors: Badgley, M. A., Kremer, D. M., Maurer, H. C., DelGiorno, K. E., Lee, H.-J., Purohit, V., Sagalovskiy, I. R., Ma, A., Kapilian, J., Firl, C. E. M., Decker, A. R., Sastra, S. A., Palermo, C. F., Andrade, L. R., Sajjakulnukit, P., Zhang, L., Tolstyka, Z. P., Hirschhorn, T., Lamb, C., Liu, T., Gu, W., Seeley, E. S., Stone, E., Georgiou, G., Manor, U., Iuga, A., Wahl, G. M., Stockwell, B. R., Lyssiotis, C. A., & Olive, K. P.
Affiliations: Columbia University Irving Medical Center (US)
University of Michigan (US)
Salk Institute for Biological Studies (US)
Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Columbia University (US)
The University of Texas at Austin (US)
University of California, San Francisco (US)
Corresponding author: Kremer, Daniel M.
Maurer, H. Carlo
Olive, Kenneth P.
ORCID: Badgley, Michael A.
Kremer, Daniel M.
Maurer, H. Carlo
DelGiorno, Kathleen E.
Lee, Ho-Joon
Purohit, Vinee
Sagalovskiy, Irina R.
Ma, Alice
Kapilian, Jonathan
Decker, Amanda R.
Palermo, Carmine F.
Andrade, Leonardo R.
Sajjakulnukit, Peter
Zhang, Li
Hirschhorn, Tal
Lamb, Candice
Liu, Tong
Gu, Wei
Stone, Everett
Georgiou, George
Manor, Uri
Iuga, Alina
Wahl, Geoffrey M.
Stockwell, Brent R.
Lyssiotis, Costas A.
Olive, Kenneth P.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2020-04-03
Volume: 368
Issue: 6486
Pages: 85-89
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aaw9872
PMC: PMC7681911
OpenAlex: W3015020891
Cited by: 1,294
References: 41
Citations by year: 2026: 165 · 2025: 206 · 2024: 253 · 2023: 230 · 2022: 210 · 2021: 171 · 2020: 58
FWCI: 94.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (T32 A009503, F31 CA180738, 1R01CA215607, P30CA013696, U24-DK097153, P01CA087497, CA189623, CA014195, R35 CA197687, Cancer Center Core Grant CA014195, CA197687)
National Cancer Institute (CA224272, R35CA209896)
Damon Runyon Cancer Research Foundation (DFS-09-14)
U.S. Department of Education
U.S. Department of Defense (W81XWH-17-1-0497)
Lustgarten Foundation (2011 Innovator Award)
Sidney Kimmel Foundation for Cancer Research (SKF-16-005)
Pancreatic Cancer Action Network (13-70-25-LYSS)
The V Foundation for Cancer Research (V2016-009)
Waitt Foundation
Salk Women and Special Science Award
The Freeberg Foundation (N/A)
Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords: ferroptosis, cysteine depletion, pancreatic cancer, lipid reactive oxygen species, cancer therapy, tumor growth inhibition
MeSH terms: Ferroptosis, Animals, Cystathionine gamma-Lyase, Cysteine, Cystine, Humans, Mice, Mutant Strains, Pancreatic Neoplasms, Gene Deletion, Carcinoma, Pancreatic Ductal, Cationic Amino Acid Transporter 1, Cell Line, Tumor, Mice

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Cysteine depletion induces pancreatic tumor ferroptosis in mice

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