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**trastuzumab + vorinostat** is a combination therapy involving the monoclonal antibody trastuzumab and the histone deacetylase inhibitor (HDACi) small molecule drug vorinostat. Trastuzumab targets human epidermal growth factor receptor 2 (HER2), which is overexpressed in certain breast cancers, and works through mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADCP). Vorinostat inhibits histone deacetylases, leading to increased acetylation of histones and other proteins, resulting in altered gene expression, immunogenic cell death, and enhanced immune response against tumor cells. When combined, these drugs have shown synergistic effects in preclinical studies by enhancing trastuzumab-mediated ADCP/ADCC activity against HER2-overexpressing cancer cells[1][3]. The combination may also increase tumor cell susceptibility to immune attack by modulating immune checkpoints such as CD47[1].
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