{
  "abstract": "Background\n\nAlmonertinib resistance poses a major challenge in treating lung adenocarcinoma (LUAD) with epidermal growth factor receptor (EGFR) mutations. Research indicates that the c-MET/PI3K/AKT signaling pathway and epithelial-mesenchymal transition (EMT) are closely associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). Anlotinib, a multi-target TKI, has demonstrated synergistic anti-tumor potential in combination with other TKIs. However, whether its combination with Almonertinib can reverse Almonertinib resistance and the underlying mechanism remain unclear.Methods\n\nAn Almonertinib-resistant cell line (NCI-H1975-AR) was established in vitro, and a xenograft model was constructed in vivo. The effect of combination therapy on cell viability, apoptosis, invasion, migration capabilities, histopathological changes and proliferation in tumor tissues were assessed. The expression of c-MET/PI3K/AKT pathway, EGFR, FGFR, and EMT markers was examined to explore the molecular mechanism of the combination therapy.Results\n\nThe combination of Anlotinib and Almonertinib significantly reduced the IC₅₀ of Almonertinib in NCI-H1975-AR cells, promoted apoptosis, and inhibited their invasion and migration capabilities. The combination treatment downregulated the expression of c-MET, p-PI3K, p-AKT, FGFR, EGFR, and Vimentin, while upregulating E-cadherin expression. The sensitizing effect of the combination treatment was partially reversed by the PI3K agonist 740 Y-P. In vivo experiments further confirmed that the combination therapy significantly inhibited tumor growth, reduced tumor volume and weight, downregulated the expression of proliferation markers CD31, PCNA, and Ki67, suppressed the c-MET/PI3K/AKT signaling pathway, downregulated EMT markers, and inhibited the expression of EGFR and FGFR.Conclusion\n\nAnlotinib combined with Almonertinib can effectively reverse Almonertinib resistance in lung adenocarcinoma by inhibiting the c-MET/PI3K/AKT signaling pathway, blocking the EMT process, and suppressing the aberrant activation of EGFR/FGFR.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Thoracic Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550008, China.",
    "Department of Oncology, Xingyi People's Hospital Affiliated to Guizhou Medical University, Xingyi, 562400, China.",
    "Department of Thoracic Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550008, China. medhealer1@163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dingdan Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Bo Peng"
    },
    {
      "affs": [
        2
      ],
      "name": "Weiwei Ouyang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/00v9xxyjceepd.bib",
  "cited_by": 0,
  "doi": "10.1186/s12957-026-04521-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13725966",
  "id": "00v9xxyjceepd",
  "issns": [
    "1477-7819"
  ],
  "landing_url": "https://europepmc.org/article/MED/42972594",
  "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": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
    ]
  ],
  "openalex": "W7172491715",
  "pdf_url": "https://europepmc.org/articles/PMC13725966?pdf=render",
  "pmcid": "PMC13725966",
  "pmid": "42972594",
  "published": "2026-08-05",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/00v9xxyjceepd.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:44Z",
      "native_id": "MED:42972594",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42972594"
    },
    {
      "first_seen": "2026-11-05T12:22:24Z",
      "native_id": "PMC13725966",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12957-026-04521-1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Lung Cancer Treatments and Mutations",
      "subfield": "general"
    }
  ],
  "title": "Anlotinib combined with almonertinib reverses almonertinib resistance in lung adenocarcinoma by inhibiting the c-MET/PI3K/AKT pathway.",
  "title_text": "Anlotinib combined with almonertinib reverses almonertinib resistance in lung adenocarcinoma by inhibiting the c-MET/PI3K/AKT pathway.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:02Z",
  "url": "https://research.draconitic.com/paper/00v9xxyjceepd",
  "venue": "World journal of surgical oncology",
  "versions": []
}