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IFNγ augments TKI efficacy by alleviating protein unfolding stress to promote GSDME-mediated pyroptosis in hepatocellular carcinoma – New Study



IFNγ augments TKI efficacy by alleviating protein unfolding stress to promote GSDME-mediated pyroptosis in hepatocellular carcinoma



Summary

Interferon-gamma (IFNγ) enhances the effectiveness of tyrosine kinase inhibitors (TKIs) in treating hepatocellular carcinoma (HCC) by mitigating protein unfolding stress within cancer cells. TKIs, while effective, often induce endoplasmic reticulum (ER) stress, leading to drug resistance. IFNγ counteracts this by reducing ER stress. This alleviates the unfolded protein response (UPR), promoting the activation of gasdermin E (GSDME)-mediated pyroptosis, a form of inflammatory cell death. Essentially, IFNγ primes HCC cells for TKI-induced pyroptosis by preventing the protective ER stress response, ultimately boosting the therapeutic impact of TKIs.

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