The topoisomerase IIa (TopIIa) inhibitor etoposide 42 combined with the Enhancer of Zeste Homologous 2 (EZH2) inhibitors 7-deazaneplanocin A (DZNep) 43 or GSK126 44 induces cell death in murine and human prostate cancer cell lines and showed therapeutic efficacy in vivo. The gene discussed is TOP2A; the disease is prostate carcinoma.