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The enhancer of zeste homolog 2 (EZH2) is a core subunit of the polycomb repressor complex 2 (PRC2), which is overexpressed in numerous cancers and mutated in several others. Notably, EZH2 acts not only a critical epigenetic repressor through its role in histone methylation, it is also an activator of gene expression, acting through multiple signaling pathways in distinct cancer types. Increasing evidence suggests that EZH2 is an oncogene and is central to initiation, growth and progression of urological cancers. In this review, we highlight the critical role of EZH2 as a master regulator of tumorigenesis in the prostate, bladder and the kidney through epigenetic control of transcription as well as a modulation of various critical signaling pathways. We also discuss the promise and challenges for EZH2 inhibitors as future anticancer therapeutics, some of which are currently in clinical trials.

Functional and therapeutic significance of EZH2 in urological cancers