One study found that IGFBP5 expression is significantly decreased in tamoxifen-resistant breast cancer cells relative to treatment-sensitive cells (110), while another showed that histone demethylase retinoblastoma-binding protein 2 (RBP2) decreases IGFBP5 expression, thereby hyperactivating the IGF signaling axis resulting in tamoxifen resistance (111). The gene discussed is IGFBP5; the disease is breast cancer.