{
  "abstract": "Non-small cell lung cancer (NSCLC) has become a biomarker-driven disease, yet durable control remains limited by therapeutic resistance, metabolic heterogeneity, and incomplete predictors of response. Cuproptosis, a copper-dependent form of regulated cell death linked to mitochondrial respiration and lipoylated TCA-cycle proteins, offers a potential metabolic layer for patient stratification. However, the current NSCLC literature is dominated by cuproptosis-related gene scores, lncRNA models, and immune-association signatures. These studies are useful for hypothesis generation but rarely demonstrate copper flux, FDX1 dependence, lipoylated DLAT/DLST engagement, iron-sulfur cluster protein loss, or pathway-specific pharmacodynamics. We therefore organize the NSCLC literature using a mechanistic evidence matrix that separates transcriptomic association, copper-access enrichment, mitochondrial-dependence evidence, canonical target engagement, and clinical pharmacodynamic confirmation. Rather than proposing a new molecular subtype or diagnostic label, we conceptualize cuproptosis susceptibility as a continuous, mechanism-based construct defined by copper access, TCA/OXPHOS dependence, lipoylated substrate burden, detoxification capacity, and immune context. This framework reframes cuproptosis from universal copper toxicity to a conditional therapeutic vulnerability. Its clinical value will depend on biomarker-enriched trials with pharmacodynamic confirmation rather than retrospective gene signatures alone.",
  "abstract_shown": true,
  "affiliations": [
    "The First Affiliated Hospital of Dalian Medical University",
    "College of Health-Preservation and Wellness, Dalian Medical University",
    "College of Integrated Chinese and Western Medicine, Dalian Medical University",
    "Department of Vascular Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University",
    "Department of Oncology, The First Affiliated Hospital of Dalian Medical University"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhanhao Liang"
    },
    {
      "affs": [
        1
      ],
      "name": "Miao Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Qinghao Song"
    },
    {
      "affs": [
        2
      ],
      "name": "Meizhu Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Yiming Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingru Jiang"
    },
    {
      "affs": [
        3
      ],
      "name": "Shibiao Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xutong Zhao"
    },
    {
      "affs": [
        4
      ],
      "name": "Yi Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8qnbb79kdfy31.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1935389",
  "fulltext_url": "https://europepmc.org/articles/PMC13688112",
  "id": "8qnbb79kdfy31",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1935389/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7220996747",
  "pdf_url": "https://europepmc.org/articles/PMC13688112?pdf=render",
  "pmcid": "PMC13688112",
  "pmid": "42923270",
  "published": "2026-10-08",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8qnbb79kdfy31.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1935389",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1935389/full"
    },
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42923270",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42923270"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Beyond gene signatures: a mechanism-based framework for cuproptosis susceptibility in non-small cell lung cancer at the metabolism–immunity interface",
  "title_text": "Beyond gene signatures: a mechanism-based framework for cuproptosis susceptibility in non-small cell lung cancer at the metabolism–immunity interface",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/8qnbb79kdfy31",
  "venue": "Frontiers in Immunology",
  "versions": []
}