Pan-Cancer Landscape and Analysis of ERBB2 Mutations Identifies Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1 Activity (Cancer Cell)

Robichaux et al. show that ERBB2 mutation hotspots vary across human tumor types, which affect the volume of the HER2 TKI binding pocket and dictate drug sensitivity. Poziotinib is the most potent HER2 TKI among those tested. Moreover, poziotinib enhances T-DM1 efficacy by increasing the cell-surface HER2 level.