Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations (Cancer Cell)

Pahuja et al. show that recurrent HER2 transmembrane domain and juxtamembrane domain mutations enhance HER2 activity by improving the active dimer interface or stabilizing an activating conformation. Importantly, HER2 inhibiting antibodies and small molecules can block the activity of these mutants.