ESR1 and breast carcinoma: RTK includes epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptor (VEGFR), insulin-like growth factor-I receptor, et al. RTKs promoted ER phosphorylation through at least two pathways: RAS–RAF–ERK and PI3K-AKT pathway (Ali and Coombes, 2002), which enabled ERα positive breast cancer cells to escape from anti-estrogen therapies.