Fig. 5: Assessment of HER2-targeted strategies.

a, b Fraction of patients with ERBB2 mutation or amplification, respectively, in bladder, UTUC and other common solid tumors in a prospectively sequenced cohort of 44,183 tumors. c Neratinib sensitivity of the UCC14-PDC (HER2 S310F-mutant UTUC), MGHU3 [ERBB2 wildtype (wt) bladder cancer], CVX-4 (HER2 S310F-mutant cervical cancer) and BT-474 (ERBB2 amplified breast cancer) was determined 5 days post-neratinib treatment. The average values from three separate experiments (n = 3) for UCC14-PDC, MGHU3, and CVX-4 and 5 separate experiments (n = 5) for BT-474 are shown. IC50s for neratinib were 508.3, 245.9, 56.8 and 0.1 nM for UCC14, MGHU3, CVX-4 and BT-474, respectively. d Inhibition of ERK and AKT, downstream HER2 effectors by neratinib. Western blot was performed (repeated three times) on samples treated with neratinib or vehicle for 1 h at the indicated concentrations. The samples were derived from the same experiment and the gels/blots were processed in parallel. e Mice with established UCC14 tumors were treated with neratinib 20 mg/kg PO daily (5 days a week), DS-8201a 10 mg/kg i.v. once every 3 weeks or vehicle only as control. Mice bearing the PDX were randomly assigned to 3 cohorts (n = 8 per each group) and monitored twice a week [P = 0.0034, vehicle vs neratinib; P < 0.0001, vehicle vs DS-8201a; P < 0.0001, neratinib vs DS-8201a]. Two-way ANOVA test (Prism) was used for statistical analysis. Data are presented as mean values ± SD. Source data for c–e are provided as a Source Data file.