ERBB2 and breast cancer: In addition, signaling though the IGF-IR has been shown to mitigate the growth inhibitory effects of trastuzumab on human breast cancer cells overexpressing ErbB2 [35]; in fact, it is becoming widely accepted that signaling through IGF-IR can contribute to resistance to ErbB2-directed therapies (reviewed in [36]), and it has been noted that a correlation between IGF-IR expression and trastuzumab resistance exists in clinical breast cancer cases [37].