NCOA2 and Familial prostate cancer: Accumulating evidence indicates that multiple factors can contribute to castration resistance, including androgen receptor, c-Myc overexpression, upregulation of PI3K/AKT and RAS/MAPK.37 ERK is frequently activated in prostate cancer samples, especially metastatic samples.38 Overexpression of nuclear receptor coactivator 2 along with loss of PTEN can result in activation of ERK, promoting tumor malignance in murine prostate tumor model.39 Thus, it is conceivable that ERK activation may contribute to castration resistance especially when tumor microenvironment becomes acidic.