{
  "abstract": "CDK4/6 inhibitors represent a key therapy for HR+/HER2- breast cancer, yet resistance and limited efficacy in triple-negative breast cancer (TNBC) remain significant challenges. Using a self-established drug combination prediction platform, we identified a strong synergy between the CDK4/6 inhibitor palbociclib and the natural compound curcumin across both HR+/HER2- and TNBC models, an effect that was also observed with ribociclib. Mechanistically, the combination led to a collapse of redox homeostasis. Despite upregulating transcriptional antioxidant responses, the treatment downregulated critical ROS-detoxifying enzymes (e.g., GPX4) and depleted glutathione. This imbalance induced lethal oxidative stress, lipid peroxidation, and extensive DNA damage. Furthermore, excessive ROS accumulation contributed to suppression of epithelial-mesenchymal transition (EMT) and reduced migratory and invasive phenotypes. The antioxidant N-acetylcysteine (NAC) attenuated both cytotoxicity and migration inhibition, supporting a central role for ROS in these effects. Together, these findings identify a redox-based mechanism underlying the combination and provide a rationale for further preclinical evaluation in HR+/HER2- breast cancer and TNBC.",
  "abstract_shown": true,
  "affiliations": [
    "School of Medicine, Institute of Infection, Immunology and Tumor Microenvironment, Wuhan University of Science and Technology, Wuhan, China.",
    "Wuhan University of Science and Technology Affiliated Wuchang Hospital, Wuhan, China.",
    "Department of Pharmacy, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.",
    "Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chenyu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yiqin Zou"
    },
    {
      "affs": [
        0
      ],
      "name": "Chunyu Chang"
    },
    {
      "affs": [
        0
      ],
      "name": "Siyue Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiankun Ke"
    },
    {
      "affs": [
        0
      ],
      "name": "Liang Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Di Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yukang Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiwen Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Sijian Huang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yilan Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenqi Yu"
    },
    {
      "affs": [
        2
      ],
      "name": "Aiping Deng"
    },
    {
      "affs": [
        2
      ],
      "name": "Ming Yue"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Jue Jiang",
      "orcid": "0009-0004-3723-8677"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/69knahghbnz43.bib",
  "cited_by": 0,
  "doi": "10.1111/cas.70557",
  "fulltext_url": "https://europepmc.org/articles/PMC13677612",
  "id": "69knahghbnz43",
  "issns": [
    "1347-9032",
    "1349-7006"
  ],
  "landing_url": "https://europepmc.org/article/MED/42893963",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Advanced Breast Cancer Therapies"
    ]
  ],
  "openalex": "W7222882415",
  "pdf_url": "https://europepmc.org/articles/PMC13677612?pdf=render",
  "pmcid": "PMC13677612",
  "pmid": "42893963",
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/69knahghbnz43.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42893963",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42893963"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Advanced Breast Cancer Therapies",
      "subfield": "general"
    }
  ],
  "title": "CDK4/6 Inhibitors and Curcumin Synergistically Suppress HER2- Breast Cancer via Lethal ROS and Inhibition of Metastasis.",
  "title_text": "CDK4/6 Inhibitors and Curcumin Synergistically Suppress HER2- Breast Cancer via Lethal ROS and Inhibition of Metastasis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/69knahghbnz43",
  "venue": "Cancer science",
  "versions": []
}