Preclinical studies in trastuzumab-resistant models demonstrate that combining STING agonists (e.g., ADU-S100) with HER2-targeted antibody-drug conjugates (e.g., DS-8201) significantly reduces the proportion of CD44+/CD24− cancer stem cells and enhances dendritic cell cross-presentation to promote CD8+ T-cell infiltration. This evidence concerns the gene CD44 and cancer.