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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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April-2026 Volume 68 Issue 4

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Review Open Access

IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)

  • Authors:
    • Qi Wei
    • Chengming Huang
    • Yuanyuan Zhang
    • Hao Zeng
    • Chang Qi
    • Sihan Tan
    • Weimin Li
    • Panwen Tian
    • Yalun Li

  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease‑related Molecular Network, Precision Medicine Center/Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Integrated Care Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
    Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 47
    |
    Published online on: February 20, 2026
       https://doi.org/10.3892/ijo.2026.5860
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Abstract

IL‑6, a pleiotropic inflammatory cytokine predominantly secreted by fibroblasts, myeloid‑derived suppressor cells, tumor‑associated macrophages and tumor cells, is associated with poor prognosis of and therapeutic resistance in non‑small cell lung cancer (NSCLC). The activation of signaling pathways, including the JAK/STAT3, MAPK and PI3K/AKT pathways, promotes tumor survival. Furthermore, the IL‑6/JAK/STAT3 signaling axis has emerged as a key driver of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKI) resistance, orchestrating intricate crosstalk within the tumor microenvironment (TME) to promote cell survival and immunosuppression. The present review synthesized current evidence on the dual role of IL‑6 in mediating EGFR‑TKI resistance and blunting anti‑tumor immunity. The present review highlights the preclinical rationale for combining IL‑6 blockade with EGFR‑TKI or immune checkpoint inhibitors to overcome refractory disease. The present review also highlights the structure, molecular mechanisms and clinical insights of IL‑6 in the TME of EGFR‑mutant NSCLC and may provide optimized therapeutic strategies for EGFR‑TKI‑refractory NSCLC.

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Copy and paste a formatted citation
Spandidos Publications style
Wei Q, Huang C, Zhang Y, Zeng H, Qi C, Tan S, Li W, Tian P and Li Y: <p>IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)</p>. Int J Oncol 68: 47, 2026.
APA
Wei, Q., Huang, C., Zhang, Y., Zeng, H., Qi, C., Tan, S. ... Li, Y. (2026). <p>IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)</p>. International Journal of Oncology, 68, 47. https://doi.org/10.3892/ijo.2026.5860
MLA
Wei, Q., Huang, C., Zhang, Y., Zeng, H., Qi, C., Tan, S., Li, W., Tian, P., Li, Y."<p>IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)</p>". International Journal of Oncology 68.4 (2026): 47.
Chicago
Wei, Q., Huang, C., Zhang, Y., Zeng, H., Qi, C., Tan, S., Li, W., Tian, P., Li, Y."<p>IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)</p>". International Journal of Oncology 68, no. 4 (2026): 47. https://doi.org/10.3892/ijo.2026.5860
Copy and paste a formatted citation
x
Spandidos Publications style
Wei Q, Huang C, Zhang Y, Zeng H, Qi C, Tan S, Li W, Tian P and Li Y: <p>IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)</p>. Int J Oncol 68: 47, 2026.
APA
Wei, Q., Huang, C., Zhang, Y., Zeng, H., Qi, C., Tan, S. ... Li, Y. (2026). <p>IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)</p>. International Journal of Oncology, 68, 47. https://doi.org/10.3892/ijo.2026.5860
MLA
Wei, Q., Huang, C., Zhang, Y., Zeng, H., Qi, C., Tan, S., Li, W., Tian, P., Li, Y."<p>IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)</p>". International Journal of Oncology 68.4 (2026): 47.
Chicago
Wei, Q., Huang, C., Zhang, Y., Zeng, H., Qi, C., Tan, S., Li, W., Tian, P., Li, Y."<p>IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review)</p>". International Journal of Oncology 68, no. 4 (2026): 47. https://doi.org/10.3892/ijo.2026.5860
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