Consistent with reports in literature that CREB activation promotes NED in prostate cancer cells [24, 28, 58], we found that CREB was up-regulated and activated (by pS133 level [59–61]) in NEPC cells NE1.3 and H660 (Figure 3A, 3B, Supplementary Figure S1). This evidence concerns the gene CREB1 and Familial prostate cancer.