{
  "abstract": "Sorafenib resistance limits the efficacy of treatments for advanced papillary thyroid carcinoma (PTC). The antitumor potential of Xiaojin Pill (XJP) has been demonstrated, yet its mechanisms potentially implicated in sorafenib resistance and combinational toxicological risks remain unclear. This study aimed to examine the molecular mechanisms through which XJP may act on signaling pathways implicated in sorafenib resistance, and to assess its combinational toxicological risks during co-administration with sorafenib. Integrating network pharmacology and toxicology, we identified XJP's active ingredients and hub targets via protein-protein interaction networks. Clinical relevance and immune infiltration were examined in cohorts from The Cancer Genome Atlas (TCGA), while molecular docking was used to explore the structural affinities. Global toxicity and metabolic drug-drug interactions (DDIs) during XJP-sorafenib co-administration were evaluated with ADMETlab 3.0. We identified 43 bioactive ingredients and 78 intersection targets, along with five hub genes (SRC, STAT3, EGFR, ERBB2, and ESR1) predicted to converge on the PI3K/Akt and MAPK pathways. Clinically, these targets correlated with poor prognosis and an immunosuppressive microenvironment. Notably, network toxicology identified a potential herb-drug interaction signal: core XJP components were predicted to bind key metabolic enzymes (CYP3A4/CYP1A2), which warrants examination in dedicated pharmacokinetic studies. Furthermore, computational analysis indicated that combination therapy may act on shared toxicological modules (Ras/Rap1), warranting attention during co-administration. In this in silico analysis, XJP was predicted to act on multiple targets converging on PI3K/Akt and MAPK signaling and was associated with immune-related signatures in PTC; these findings provide a basis for further investigation. However, CYP-mediated metabolic interference may represent a potential herb-drug interaction that warrants attention in future pharmacokinetic studies.",
  "abstract_shown": true,
  "affiliations": [
    "The First Clinical Medical College, Wenzhou Medical University, Wenzhou, China.",
    "Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.",
    "Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.",
    "Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.",
    "Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Provincial People's Hospital), Wenzhou, China.",
    "The Alberta Institute, Wenzhou Medical University, Wenzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Junhao Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiajun Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaibo Su"
    },
    {
      "affs": [
        1
      ],
      "name": "Qingxuan Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Chunjue Ni"
    },
    {
      "affs": [
        3
      ],
      "name": "Endong Chen"
    },
    {
      "affs": [
        4
      ],
      "name": "Boxi Wang"
    },
    {
      "affs": [
        5
      ],
      "name": "Man Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhaokai Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "Yihan Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Huazhen Mei"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianyu Han"
    },
    {
      "affs": [
        0
      ],
      "name": "Haozhuo Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yefeng Cai"
    },
    {
      "affs": [
        3
      ],
      "name": "Quan Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b8eg75gpaxjw8.bib",
  "cited_by": 0,
  "doi": "10.21037/tcr-2026-2690",
  "fulltext_url": "https://europepmc.org/articles/PMC13743226",
  "id": "b8eg75gpaxjw8",
  "issns": [
    "2218-676X",
    "2219-6803"
  ],
  "landing_url": "https://europepmc.org/article/MED/42997877",
  "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",
      "3002|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W7224096058",
  "pdf_url": "https://europepmc.org/articles/PMC13743226?pdf=render",
  "pmcid": "PMC13743226",
  "pmid": "42997877",
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b8eg75gpaxjw8.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "MED:42997877",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42997877"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:3002|Computational Drug Discovery Methods",
      "subfield": "medicinal"
    }
  ],
  "title": "The pharmacological potential and metabolic risks of Xiaojin Pill in sorafenib-resistant papillary thyroid carcinoma: an integrated network analysis.",
  "title_text": "The pharmacological potential and metabolic risks of Xiaojin Pill in sorafenib-resistant papillary thyroid carcinoma: an integrated network analysis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/b8eg75gpaxjw8",
  "venue": "Translational cancer research",
  "versions": []
}