These findings reveal the IFI16-CXCL10/11 signaling pathway as the crucial pathway conferring anti-HER2 trastuzumab resistance, and this pathway can be epigenetically targeted by EZH2 and HDAC inhibitor combination therapy to induce complete tumor eradication through increased CD8 + T-cell infiltration and induction of long-term T-cell memory in HER2+ breast cancer [251]. The gene discussed is IFI16; the disease is breast carcinoma.