{
  "abstract": "Cellular heterogeneity and plasticity are hallmarks of cancer that contribute to tumor growth and therapy resistance. Here, we investigated metabolic heterogeneity in small cell lung cancer (SCLC), an aggressive cancer type with considerable plasticity between neuroendocrine (NE) and non-NE cellular states. Through integrated transcriptomic and metabolomic analyses, we identified a universal dependency on exogenous cysteine/cystine (Cys) across all NE/non-NE SCLC cell states. Notably, NE and non-NE cells with low ASCL1 transcription factor levels underwent ferroptosis upon Cys depletion, whereas ASCL1 high cells underwent apoptosis while remaining resistant to ferroptosis. This ferroptosis resistance was driven by the direct transcriptional activation of GCH1 by ASCL1, resulting in increased levels of the antioxidants BH4/BH2. Accordingly, combined Cys depletion and inhibition of BH4/BH2 synthesis reduced tumor growth in patient-derived xenografts. These findings demonstrate that metabolic state influences cell-death susceptibility in SCLC and provide a rationale for therapeutic strategies that exploit these metabolic differences.",
  "abstract_shown": true,
  "affiliations": [
    "Departments of Pediatrics, Stanford University, Stanford, CA, USA",
    "Departments of Genetics, Stanford University, Stanford, CA, USA",
    "These authors contributed equally",
    "Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany",
    "CECAD Cluster of Excellence, University of Cologne, Cologne, Germany",
    "Sarafan ChEM-H, Stanford University, Stanford, CA, USA",
    "Department of Radiation Oncology, Radiation and Cancer Biology, Stanford University, Stanford, CA, USA.",
    "Institute for Metabolomics in Ageing, Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany",
    "Institute of Genetics, Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Faculty of Mathematics and Natural Sciences, Cologne, Germany",
    "Department of Biology, Stanford University, Stanford, CA, USA",
    "Waters Corporation, Milford, MA, USA",
    "University of Cologne, Faculty of Medicine, Institute of Medical Statistics and Computational Biology, Cologne",
    "Department of Metabolism and Physiology, Moffitt Cancer Center, Tampa, FL, USA",
    "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA",
    "Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA",
    "Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, Cologne, Germany",
    "Lead contact"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 33,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jun W. Kim"
    },
    {
      "affs": [
        0,
        1,
        3,
        4,
        2
      ],
      "name": "Christina M. Bebber"
    },
    {
      "affs": [
        5
      ],
      "name": "Yuqin Dai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sarah Bopp"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Anna Edenhofer"
    },
    {
      "affs": [
        6
      ],
      "name": "Albert M. Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Thomas Rösner"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lena Berning"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Ming Yang"
    },
    {
      "affs": [
        9
      ],
      "name": "Logan B. Leak"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Jenny Stroh"
    },
    {
      "affs": [
        10
      ],
      "name": "Bindesh Shrestha"
    },
    {
      "affs": [
        4,
        11
      ],
      "name": "Ali T. Abdallah"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Dimitrios Prymidis"
    },
    {
      "affs": [
        10
      ],
      "name": "Hernando J. Olivos"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Maya Baron"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Thuyen Nguyen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yan Ting Shue"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yoko Nishiga"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alexandros P. Drainas"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Andrea C. Chaikovsky"
    },
    {
      "affs": [
        0,
        1,
        9
      ],
      "name": "Krystina Szylo"
    },
    {
      "affs": [
        6
      ],
      "name": "Yang Li"
    },
    {
      "affs": [
        12
      ],
      "name": "Yun P. Kang"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Parvathy Manoj"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Alvaro Quintanal Villalonga"
    },
    {
      "affs": [
        13,
        14
      ],
      "name": "Charles M. Rudin"
    },
    {
      "affs": [
        12
      ],
      "name": "Gina M. DeNicola"
    },
    {
      "affs": [
        9
      ],
      "name": "Scott J. Dixon"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Christian Frezza"
    },
    {
      "affs": [
        6
      ],
      "name": "Jiangbin Ye"
    },
    {
      "affs": [
        3,
        4,
        15
      ],
      "name": "Silvia von Karstedt"
    },
    {
      "affs": [
        0,
        1,
        16
      ],
      "name": "Julien Sage"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/93h68vp0ja0xf.bib",
  "cited_by": 0,
  "doi": "10.1016/j.cell.2026.09.045",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13718723/",
  "id": "93h68vp0ja0xf",
  "issns": [
    "0092-8674",
    "1097-4172"
  ],
  "landing_url": "https://doi.org/10.1016/j.cell.2026.09.045",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7223291267",
  "pdf_url": null,
  "pmcid": "PMC13718723",
  "pmid": "42914976",
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/93h68vp0ja0xf.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:22:41Z",
      "native_id": "PMC13718723",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.cell.2026.09.045"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Cell state-specific metabolic networks govern ferroptosis versus apoptosis in small cell lung cancer",
  "title_text": "Cell state-specific metabolic networks govern ferroptosis versus apoptosis in small cell lung cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:41Z",
  "url": "https://research.draconitic.com/paper/93h68vp0ja0xf",
  "venue": "Cell",
  "versions": []
}