{
  "abstract": "NRF2 (nuclear factor erythroid 2-related factor 2) and its repressor KEAP1 (Kelch-like ECH-associated protein 1) govern the antioxidant response; their role in breast cancer is paradoxical: the same program that prevents malignant transformation can later drive survival and therapy resistance. We argue that this behavior is not a fixed switch but a continuum conditioned by molecular subtype, disease stage, and therapeutic context. Synthesizing primary mechanistic and clinical evidence, we find that NRF2 activation is predominantly non-mutational and that its pathological dependence is strongest not in triple-negative breast cancer (TNBC) as a whole but in a candidate redox-addicted subset-defined by nuclear NRF2 with reduced cytoplasmic KEAP1 protein, cystine/SLC7A11 reliance, and active ferroptosis defense. This subset is hypothesis-generating rather than validated: current support derives chiefly from a single tissue microarray cohort and cell-line studies, and the co-occurrence and prevalence of its features remain unestablished. NRF2-driven suppression of ferroptosis is one major, tractable mechanism of resistance among several. We frame these as directions for future research: no NRF2-directed intervention is ready for biomarker-guided selection, and systemic NRF2 inhibition risks on-target toxicity, because NRF2 also protects normal tissues from oxidative stress.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiology, Gyeongsang National University Hospital and College of Medicine, 79 Gangnam-ro, Jinju 52727, Republic of Korea.",
    "Department of Radiology, Gyeongsang National University College of Medicine, 816-15 Jinju-daero, Jinju 52727, Republic of Korea.",
    "Institute of Medical Science, Gyeongsang National University College of Medicine, 816-15 Jinju-daero, Jinju 52727, Republic of Korea.",
    "Biomedical Research Institute, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 52727, Republic of Korea."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hye Young Choi",
      "orcid": "0000-0002-3714-5700"
    },
    {
      "affs": [
        2
      ],
      "name": "Hayeong Kwon",
      "orcid": "0000-0002-8828-6060"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Young-Sool Hah",
      "orcid": "0000-0002-8571-2722"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5yn264e4sdfj2.bib",
  "cited_by": 0,
  "doi": "10.3390/antiox15101223",
  "fulltext_url": "https://europepmc.org/articles/PMC13700803",
  "id": "5yn264e4sdfj2",
  "issns": [
    "2076-3921"
  ],
  "landing_url": "https://europepmc.org/article/MED/42939797",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Genomics, phytochemicals, and oxidative stress"
    ]
  ],
  "openalex": "W7214034609",
  "pdf_url": "https://europepmc.org/articles/PMC13700803?pdf=render",
  "pmcid": "PMC13700803",
  "pmid": "42939797",
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5yn264e4sdfj2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42939797",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42939797"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics, phytochemicals, and oxidative stress",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Subtype-Conditioned NRF2-KEAP1 Signaling in Breast Cancer: A Narrative Review and Hypothesis-Generating Framework from Chemoprevention to Therapy Resistance.",
  "title_text": "Subtype-Conditioned NRF2-KEAP1 Signaling in Breast Cancer: A Narrative Review and Hypothesis-Generating Framework from Chemoprevention to Therapy Resistance.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/5yn264e4sdfj2",
  "venue": "Antioxidants (Basel, Switzerland)",
  "versions": []
}