A detailed understanding of interplay between genetics and epigenetics in the progression and hormone dependence of distinct cancer subtypes is critical to the development of new approaches to prevention and therapy. Steroid hormones and their receptors play essential roles in the development and progression of both breast and prostate cancers. It remains unknown what role an epigenetically defined cell of origin plays in determining hormone responsiveness. In addition whether acquired resistance to endocrine therapy is the result of clonal evolution or the presence of hormone independent tumor-initiating cells, or both remains to be determined. Gain of function mutations and gene amplification of the androgen receptor (AR) in prostate cancer and the estrogen receptor (ER) in breast cancer in a subset of hormone refractory cases supports clonal evolution as the dominant mechanism of resistance in in these patients. We have investigated how the pathways downstream of AR and ER are activated in cases where they are not genetically altered and whether these depend on mutations in other epigenetic regulators including other transcription factors involved in steroid receptor networks and chromatin modifying enzymes involved in transcriptional regulation mediated by these receptors. Renewed success in targeting the steroid receptors themselves and promising advances in inhibiting the activity of the chromatin modifying enzymes provides new opportunities for the treatment of patients with breast and prostate cancer.

Citation Format: Myles Brown. Epigenetics of hormone dependence. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr IA15.