We have shown that the fully human anti-HER3 monoclonal Ab MM-121 (Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA), inhibiting ligand-dependent activation of HER3 [21, 22], is able to abrogate drug resistance and significantly enhance the antitumor activity of trastuzumab and paclitaxel against HER2-overexpressing breast cancer in vitro and in vivo [16, 23, 24]. This evidence concerns the gene ERBB3 and breast cancer.