Since activation of the PI-3 K/Akt signaling is the major determinant of treatment resistance [29], we investigated, in vitro and in vivo, whether the anti-erbB3 Ab MM-121 would be able to overcome resistance and enhance the efficacy of chemotherapy or trastuzumab against erbB2-overexpressing breast cancer models via inhibition of the erbB3/PI-3 K/Akt signaling. This evidence concerns the gene ERBB2 and breast cancer.