Histone Deacetylase Functions in Gastric Cancer: Therapeutic Target?

Cancers (Basel). 2022 Nov 7;14(21):5472. doi: 10.3390/cancers14215472.


Gastric cancer (GC) is one of the most aggressive cancers. Therapeutic treatments are based on surgery combined with chemotherapy using a combination of platinum-based agents. However, at metastatic stages of the disease, survival is extremely low due to late diagnosis and resistance mechanisms to chemotherapies. The development of new classifications has not yet identified new prognostic markers for clinical use. The studies of epigenetic processes highlighted the implication of histone acetylation status, regulated by histone acetyltransferases (HATs) and by histone deacetylases (HDACs), in cancer development. In this way, inhibitors of HDACs (HDACis) have been developed and some of them have already been clinically approved to treat T-cell lymphoma and multiple myeloma. In this review, we summarize the regulations and functions of eighteen HDACs in GC, describing their known targets, involved cellular processes, associated clinicopathological features, and impact on survival of patients. Additionally, we resume the in vitro, pre-clinical, and clinical trials of four HDACis approved by Food and Drug Administration (FDA) in cancers in the context of GC.

Keywords: biomarker; gastric cancer; histone deacetylase; histone deacetylase inhibitor.

Publication types

  • Review

Grant support

This research was financially supported by the Centre National pour la Recherche Scientifique (CNRS, France; C.G.), the Conférence de Coordination Interrégionale Grand Est-Bourgogne Franche-Comté de la Ligue Contre le Cancer and the Institut de cancérologie Strasbourg Europe. The Streinth Team is also supported by the Association pour la Recherche sur le Cancer, ITMO Cancer, European action COST Proteocure, the Interdisciplinary thematic Institute InnoVec, the IDEX Excellence grant from Unistra, and the Institut National du Cancer. B.A. supported by a PhD fellowship awarded by the French association “Ligue Contre le Cancer”.