Our studies of urothelial cancer organoids derived from tumors classified clinically as ERBB2 amplified revealed that these models lacked the HER2 oncogenic dependence characteristic of HER2 amplified breast cancer cells, with higher concentrations of neratinib required to inhibit downstream effectors of HER2 signaling including ERK and AKT. The gene discussed is AKT1; the disease is breast carcinoma.