Endometrial carcinoma is the most common malignant
tumor of the female genital tract in the United States. Epigenetic alterations are implicated in
endometrial cancer development and progression.
Histone deacetylase inhibitors are a novel class of anticancer drugs that increase the level of
histone acetylation in many cell types, thereby inducing cell cycle arrest, differentiation, and apoptotic cell death. This review is aimed at determining the role of
histone acetylation and examining the therapeutic potential of
histone deacetylase inhibitors in
endometrial cancer. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms
histone deacetylase,
histone deacetylase inhibitor, and
endometrial cancer were employed, and we were able to identify fifty-two studies focused on
endometrial carcinoma and published between 2001 and 2021. Deregulation of
histone acetylation is involved in the
tumorigenesis of both
endometrial carcinoma histological types and accounts for high-grade, aggressive
carcinomas with worse prognosis and decreased overall survival.
Histone deacetylase inhibitors inhibit
tumor growth, enhance the transcription of silenced physiologic genes, and induce cell cycle arrest and apoptosis in
endometrial carcinoma cells both in vitro and in vivo. The combination of
histone deacetylase inhibitors with traditional chemotherapeutic agents shows synergistic cytotoxic effects in
endometrial carcinoma cells.
Histone acetylation plays an important role in
endometrial carcinoma development and progression.
Histone deacetylase inhibitors show potent antitumor effects in various
endometrial cancer cell lines as well as
tumor xenograft models. Additional clinical trials are however needed to verify the clinical utility and safety of these promising therapeutic agents in the treatment of patients with
endometrial cancer.