TOP2A and EZH2 might be biomarkers of disease with increased metastatic potential, according to a genome-wide analysis of data from nine cohorts of patients with primary or metastatic castration-resistant prostate cancer, and one prospective cohort. In addition, in prostate cancer mouse cell line models, concurrent increase of TOP2A and EZH2 led to hypersensitivity to treatment with a combination of the topisomerase II inhibitor etoposide and inhibitors of EZH2.