The KDM4 subfamily H3K9 histone demethylases are epigenetic regulators that control chromatin structure and gene expression by demethylating histone H3K9, H3K36, and H1.4K26. The KDM4 subfamily mainly consists of four proteins (KDM4A‐D), all harboring the Jumonji C domain (JmjC) but with differential substrate specificities. KDM4A‐C proteins also possess the double PHD and Tudor domains, whereas KDM4D lacks these domains. KDM4 proteins are overexpressed or deregulated in multiple cancers, cardiovascular diseases, and mental retardation and are thus potential therapeutic targets. Despite extensive efforts, however, there are very few KDM4‐selective inhibitors. Defining the exact physiological and oncogenic functions of KDM4 demethylase will provide the foundation for the discovery of novel potent inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM4s and the interplay between KDM4‐mediated epigenetic and metabolic pathways in cancer. We also review currently available KDM4 inhibitors and discuss their potential as therapeutic agents for cancer treatment.

Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM3A in cancer. We also discuss existing KDM3A-related inhibitors and review their potential as therapeutic agents for overcoming cancer.

Trichrome vitiligo is a variant of active vitiligo. The changes of melanocytes, keratinocytes, and Langerhans cells may be involved in the pathogenesis of depigmentation in trichrome vitiligo.

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