Supplementary Figures S1-S3 from Trastuzumab Deruxtecan Resistance via Loss of HER2 Expression and Binding

Supplementary Figure S1 shows FISH imaging of V597M patient; ddPCR of HER2 WT and V597M OE model; pHrodo labeling principle and data analysis; WB, qPCR, T-DXd internalization and cell growth curves of HER2 WT vs Q213* models; MD simulation, WB,FACS, T-DXd internalization and cell growth curves of HER2 WT vs P593R model. Supplementary Figure S2 shows impact of HER2 expressions on T-DXd internalization and efficacy across various cell lines models; workflow of ELISA experiment and quantification of extracellular Trastuzumab. Supplementary Figure S3 shows WB and IHC staining of TROP2 expression in different cell lines/PDX 57aS1; cell growth curves of T-DXd, Dato-DXd and their combination in different cell line models; Internalization of different concentrations of pHrodo labeled T-DXd and Dato-DXd in MCF10A HER2 OE cells; In vivo efficacy of T-DXd, Dato-DXd and their combination in PDX 18cS1 model; Body weight of each mouse treated with single high dose of T-DXd vs low doses of T-DXd + Dato-DXd.