What is it about?
HER2 targeted antibody treatment, such as trastuzumab (Herceptin), has significantly increased the clinical responses of HER2+ breast cancer. Despite of its initial response, up to 50% of the HER2+ breast cancer patients develop resistance to the treatment, followed by disease progression, relapse, and metastasis. We have identified IFI16-dependent STING immune signaling pathway as an important immune cascade contributing to anti-HER2 antibody resistance. It also serves as a biomarker signature to identify HER2+ patients with the potential of developing resistance to the anti-HER2 antibody targeted treatment. To this end, we have provided an actionable epigenetic approach to restore IFI16-STING pathway and to reactivate the immunotherapeutic efficacy of trastuzumab. Significantly, the combinatory treatment promotes the IFI16-mediated CXCL10/11 signaling for complete tumor eradication, and long-term CD8+ T cell memory in HER2+ breast cancer.
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Why is it important?
Our biomarkers identified HER2+ breast cancer patients with potential of developing resistance or showing low responsiveness towards anti-HER2 antibody treatment. Targeting one of the biomarkers, IFI16, we have provided an actionable epigenetic approach for achieving complete and durable tumor remissions, and long-term immune memory in HER2+ breast cancer. This treatment could increase the clinical outcomes and long term efficacy of anti-HER2 antibody treatment.
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This page is a summary of: IFI16-dependent STING signaling is a crucial regulator of anti-HER2 immune response in HER2+ breast cancer, Proceedings of the National Academy of Sciences, July 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2201376119.
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