Before generating HER2-directed ADC-resistant cell lines, we first tested the antitumor effects of T-DM1 and T-DXd in xenograft models and confirmed that single-agent treatment led to tumor shrinkage in both SUM190 (-66.84% GI and -25.56% GI respectively, P < 0.001) and HCC1954 (-18.60% GI and -22.82% GI respectively, P < 0.05) xenografts compared to in vehicle control (Fig. S1C). The gene discussed is ERBB2; the disease is neoplasm.