ERBB2 and breast cancer: However, the downregulated expression of IGFBP-3 mediated the resistance to gefitinib in A431 squamous cancer cells [84], reduced the apoptosis of antiestrogen-resistant breast cancer cells to ICI 182,780 [85], increased the resistance to trastuzumab therapy in HER2 positive breast cancer [86], and reduced tumor sensitivity to molecular-targeted therapies in NSCLC [87].