This research examines the complex roles of IL-6 in the context of cancer, including its action on tumor cells and tumor microenvironment via modulation of immune, stroma cells, and endothelial cells. IL-6 mediates its tumor-supportive action mainly via traditional and trans-signaling, with tumor growth, immune evasion, and survival of tumor cells being its consequences. Elevated circulating levels of IL-6 correlate with more advanced disease and enhanced resistance against treatment, highlighting its importance as a target for treatment. Existing treatment modalities include anti-IL-6 and anti-IL-6 receptor monoclonal antibodies, with small molecule JAK1/2 and STAT3 downstream targets. The complex and redundant mechanisms of IL-6, however, challenge treatment efficacy. This review contextualizes the novel advancements in IL-6 target therapies and discusses combinatorial approaches under investigation to circumvent resistance and improve clinical outcomes.
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Zhou et al. (2025) studied this question.
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