EGF and Familial prostate cancer: In addition, in castration-resistant prostate cancers, androgens transcriptionally upregulate receptors for IGF-I and epidermal growth factor (EGF), that are key drivers of the PI3K signalling pathway [112] These effects culminate in crosstalk and feedback loops occurring between RTKs, androgen and estrogen signaling and the PI3K/Akt/mTOR signaling cascade [113,114].