Epigenetic regulators such as KDM1A, KDM3A, KDM5A, KDM6A, KDM7A, EZH2, DOT1L, and others have been shown to be critical in oncogenesis and cancer resistance.3,32,33 The discovery of the specific role of KDM3A in the interplay between a tissue-specific steroid receptor transcription factor and metabolic signaling provides a foundation for rational design of combination approaches where metabolic, epigenetic, and hormone-deprivation therapies may synergize. This evidence concerns the gene DOT1L and cancer.