However, HER2 dependent blockade of PI3K/Akt proteins can lead to compensatory activation of the MAPK/ERK signaling pathway.57 Importantly, various studies have shown limited inhibitory activity of trastuzumab on HER2 activation/autophosphorylation in HER2pos BC.58 Our study provides molecular evidence that HER2-DC1 i.t. and anti-HER2 antibodies combination treatment remarkably inhibited expression and activation/autophosphorylation of HER2, resulting in diminished activation of HER2-mediated signaling proteins Akt, JAK2, STAT3, STAT5, MAPK and ERK in the HER2pos BC model. The gene discussed is STAT3; the disease is breast cancer.