We have an ongoing interest in the role of methylation changes in cancer as well as the roles of androgen and estrogen receptor signaling in prostate and breast cancer. We demonstrated that in castration-resistant prostate cancer, androgen receptor signaling still plays a major role, but that the binding sites are substantially remodeled (Decker et al, 2012). Further we have shown that amplification of the estrogen-receptor is one potential mechanism amongst various mutations and fusions by which estrogen receptor is over-expressed in endocrine therapy resistant breast cancer (Li et al. 2013). Lastly, we mapped DNA methylation genome-wide in endocrine therapy resistant breast cancer and demonstrated that epigenetic activation of the EP4 receptor was required for estrogen-independent cell proliferation (Hiken et al. 2017).