The observed p.S239P mutation resides in ERBB4 extracellular dimerizing domain, has formerly been reported in esophageal cancer as ERBB4-activating mutation [45] and might represent a bypass-mechanism for erlotinib-resistance, but the role of ERBB4-mutants in TKI-resistance needs further clarification. This evidence concerns the gene ERBB4 and esophageal cancer.