Indeed, our recent studies with the unique trastuzumab-resistant breast cancer model demonstrate that the erbB3 receptor interacts with both erbB2 and the insulin-like growth factor-1 receptor (IGF-1R) to form a heterotrimeric complex, which mainly activates the PI-3K/Akt signaling and Src kinase and subsequently leads to trastuzumab resistance [26]. Here, IGF1R is linked to breast cancer.