Calibasi-Kocal G. Inflammatory cytokine-associated cisplatin resistance in non-small cell lung cancer and re-sensitization through interleukin-6 receptor blockade. World J Clin Oncol 2025; 16(12): 114275 [DOI: 10.5306/wjco.v16.i12.114275]
Corresponding Author of This Article
Gizem Calibasi-Kocal, PhD, Department of Translational Oncology, Institute of Oncology, Dokuz Eylul University, Cumhuriyet Bulvarı 144, Alsancak, Izmir 35330, Türkiye. gizem.calibasi@deu.edu.tr
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Oncology
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 24, 2025 (publication date) through Dec 30, 2025
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World Journal of Clinical Oncology
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2218-4333
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Calibasi-Kocal G. Inflammatory cytokine-associated cisplatin resistance in non-small cell lung cancer and re-sensitization through interleukin-6 receptor blockade. World J Clin Oncol 2025; 16(12): 114275 [DOI: 10.5306/wjco.v16.i12.114275]
World J Clin Oncol. Dec 24, 2025; 16(12): 114275 Published online Dec 24, 2025. doi: 10.5306/wjco.v16.i12.114275
Inflammatory cytokine-associated cisplatin resistance in non-small cell lung cancer and re-sensitization through interleukin-6 receptor blockade
Gizem Calibasi-Kocal
Gizem Calibasi-Kocal, Department of Translational Oncology, Institute of Oncology, Dokuz Eylul University, Izmir 35330, Türkiye
Author contributions: Calibasi-Kocal G conceived the overall concept, developed the manuscript outline, contributed to the discussion and design, conducted the literature review, and drafted, revised, and edited the manuscript.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Gizem Calibasi-Kocal, PhD, Department of Translational Oncology, Institute of Oncology, Dokuz Eylul University, Cumhuriyet Bulvarı 144, Alsancak, Izmir 35330, Türkiye. gizem.calibasi@deu.edu.tr
Received: September 15, 2025 Revised: October 6, 2025 Accepted: December 19, 2025 Published online: December 24, 2025 Processing time: 99 Days and 6.9 Hours
Abstract
Chemoresistance remains a major challenge in non-small cell lung cancer, especially for cisplatin (DDP)-based therapies, which are a mainstay of treatment. In their study, Dai et al investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance. By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines (A549/ DDP and SK-MES-1/DDP), the authors show that increased levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α are linked to resistance. Logistic regression identifies IL-6 and IL-8 as key risk factors. Functional experiments using tocilizumab, an IL-6 receptor antagonist, demonstrate a reduction in DDP half maximum inhibitory concentration, higher apoptosis rates, and decreased migration and invasion in resistant cells. Although the study has certain limitations, such as the analysis of only five inflammatory cytokines in a small, non-stratified patient cohort; it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance. Overall, the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.
Core Tip: Dai et al’s research study explores the association between inflammatory cytokines and cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC). Elevated levels of interleukin (IL)-6 and IL-8 were identified as key risk factors contributing to cisplatin resistance in NSCLC. Notably, IL-6 inhibition via the receptor antagonist tocilizumab restored DDP sensitivity and attenuated malignant phenotypes in resistant cell lines, by reducing cell viability, migration, and invasion, while enhancing apoptosis. These findings highlight the tumor microenvironment-cytokine interplay, particularly IL-6 signaling, as a critical determinant and potential therapeutic avenue in overcoming DDP resistance in NSCLC.
