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 [PMID: 41480163 DOI: 10.5306/wjco.v16.i12.114275]
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08888552
Submitted on:
December 26, 2025, 02:04
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Reader Comments:
1.The article does not cover the temporal and spatial dynamic changes of inflammatory cytokines during the development of NSCLC, as well as how these changes affect the occurrence and development of drug resistance. For instance, are there any differences in the expression levels of inflammatory cytokines in the early stage, progression stage, and resistance stage of the tumor? Are their distributions different in various parts of the tumor (such as the primary lesion and metastatic lesion)?
It is suggested to utilize techniques such as in situ hybridization and immunohistochemistry, combined with single-cell sequencing and spatial transcriptomics, to study the temporal and spatial dynamic changes of inflammatory cytokines in different development stages and different locations of NSCLC. By analyzing longitudinal samples of patients (such as before treatment, during treatment, and after resistance), the dynamic change patterns of inflammatory cytokines during the process of drug resistance can be revealed.
2. Although IL-6R blockade shows the effect of reversing drug resistance, single-target therapy may have limitations in efficacy or the risk of drug resistance escape. It is suggested to explore IL-6/IL-8 dual-target inhibition in preclinical models, or to combine it with downstream pathway inhibitors (such as JAK/STAT, PI3K/AKT, NF-κB inhibitors) or immune checkpoint inhibitors to evaluate its synergistic anti-tumor effect and its remodeling effect on the tumor microenvironment, in order to provide theoretical basis for future clinical trials of combination therapy.