These findings suggest that apoptosis is induced in response to afatinib in the SAS cell line carrying the activating HER4 G1109C mutation through the inhibition of the HER4 signal....Our experimental findings revealed that the HER4 G1109C mutation is an activating oncogenic mutation with a transformational ability and that afatinib was effective against an HER4 G1109C-mutated HNSCC cell line by inhibiting the HER4 signal, both in vitro and in vivo.