Various resistance mechanisms of anti-HER2 therapy have been suggested, including upregulation of ligands, increased signalling from other HER family receptors and loss of phosphatase and tensin homologue (PTEN) with activation of the PI3K pathway.13–15 These mechanisms suggest that persistent HER2 signal activation can be one of the major drivers of tumour proliferation after trastuzumab failure. The gene discussed is ERBB2; the disease is neoplasm.