EZH2 and metastatic prostate carcinoma: Other rational therapeutic strategies are being pursued, targeting continued AR signalling; AR cofactors, for example, P300; PI3K/AKT signalling; the PRC2 complex protein including EZH2; as well as novel synthetic lethal strategies.<h4>Conclusions and clinical implications</h4>A rapidly evolving standard of care is anticipated for metastatic prostate cancer, making it imperative that rational registration trial designs incorporating multipurpose biomarkers to accelerate anticancer drug development are pursued.