Lysine-specific demethylase 4 A (KDM4A

also named JMJD2A

KIA0677

or JHDM3A) is a demethylase that can remove methyl groups from histones H3K9me2/3

H3K36me2/3

and H1.4K26me2/me3. Accumulating evidence suggests that KDM4A is not only involved in body homeostasis (such as cell proliferation

migration and differentiation

and tissue development) but also associated with multiple human diseases

especially cancers. Recently

an increasing number of studies have shown that pharmacological inhibition of KDM4A significantly attenuates tumor progression

in vitro

and

in vivo

in a range of solid tumors and acute myeloid leukemia. Although there are several reviews on the roles of the KDM4 subfamily in cancer development and therapy

all of them only briefly introduce the roles of KDM4A in cancer without systematically summarizing the specific mechanisms of KDM4A in various physiological and pathological processes

especially in tumorigenesis

which greatly limits advances in the understanding of the roles of KDM4A in a variety of cancers

discovering targeted selective KDM4A inhibitors

and exploring the adaptive profiles of KDM4A antagonists. Herein

we present the structure and functions of KDM4A

simply outline the functions of KDM4A in homeostasis and non-cancer diseases

summarize the role of KDM4A and its distinct target genes in the development of a variety of cancers

systematically classify KDM4A inhibitors

summarize the difficulties encountered in the research of KDM4A and the discovery of related drugs

and provide the corresponding solutions

which would contribute to understanding the recent research trends on KDM4A and advancing the progression of KDM4A as a drug target in cancer therapy.