{
  "abstract": "BRCA1-mutant breast cancer is characterized by homologous recombination deficiency and genomic instability. Although these tumors are initially sensitive to platinum-based chemotherapy and PARP inhibitors, acquired treatment resistance remains a major clinical challenge. Ferroptosis is a potential therapeutic vulnerability, but the role of the SLC7A11/xCT–ferroptosis axis in this disease remains unclear. Current evidence does not establish whether increased SLC7A11 expression is a causal determinant of platinum- or PARP inhibitor resistance or a secondary response to treatment-induced stress; functional evidence directly linking SLC7A11 manipulation to drug resistance in genotype-defined BRCA1-mutant breast cancer remains limited. This review examines evidence linking SLC7A11-mediated cystine utilization to glutathione synthesis, GPX4-dependent antioxidant defense, redox and metabolic adaptation, and treatment response. We distinguish findings from BRCA1-mutant or BRCA1-deficient models from those in non-stratified breast cancer, TNBC, and broader cancer models, and discuss crosstalk with DNA damage responses and the tumor microenvironment. Individual studies have implicated VDAC3 in erastin response. BRCA1/BARD1-dependent GPX4 regulation has also been linked to ferroptosis control. However, these mechanisms require independent validation. Glucose restriction may produce overlapping but mechanistically separable ferroptotic and disulfidptotic phenotypes in SLC7A11-high cells; direct evidence for disulfidptosis in BRCA1-mutant breast cancer is lacking. Potential therapeutic strategies targeting SLC7A11, NRF2/ATF4 signaling, GPX4-related defenses, NADPH regeneration, glucose metabolism, and stromal or immune–metabolic interactions are reviewed. However, most SLC7A11-centered mechanistic and therapeutic evidence remains preclinical and has not been systematically validated in genotype-defined, platinum- or PARP inhibitor-resistant BRCA1-mutant breast cancer models. Future studies should prioritize biomarker-guided evaluation, pathway-selective experiments to distinguish ferroptosis from disulfidptosis, and prospective validation in treatment-resistant BRCA1-mutant models and clinical cohorts.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Review",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Yuying Yang"
    },
    {
      "name": "Yu Li"
    },
    {
      "name": "Xiaoyu Hao"
    },
    {
      "name": "Wenwen Yan"
    },
    {
      "name": "Xiaodong Ma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7k94fq3qwk5hz.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1985224",
  "fulltext_url": null,
  "id": "7k94fq3qwk5hz",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1985224",
  "language": null,
  "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": [
    [
      "feed-journal",
      "medicine/oncology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/7k94fq3qwk5hz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.3389/fonc.2026.1985224",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1985224"
    },
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "10.3389/fonc.2026.1985224",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1985224/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/oncology",
      "subfield": "oncology"
    }
  ],
  "title": "The SLC7A11–ferroptosis axis in BRCA1-mutant breast cancer: current mechanistic evidence, potential therapeutic vulnerabilities, and translational perspectives",
  "title_text": "The SLC7A11–ferroptosis axis in BRCA1-mutant breast cancer: current mechanistic evidence, potential therapeutic vulnerabilities, and translational perspectives",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T00:21:05Z",
  "url": "https://research.draconitic.com/paper/7k94fq3qwk5hz",
  "venue": "Frontiers in Oncology",
  "versions": []
}