Rapidly evolving investigational strategies-including bipolar androgen therapy (BAT), immunotherapeutic approaches for <i>CDK12</i>-altered tumors, targeted interventions for <i>SPOP</i>-mutated cancers, and epigenetic modulation such as EZH2 inhibition for neuroendocrine prostate cancer-further illuminate mechanisms of tumor evolution, lineage plasticity, and treatment resistance. This evidence concerns the gene EZH2 and neoplasm.