Histone Deacetylase Functions in Gastric Cancer: Therapeutic Target?

Abstract

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.

Pan-cancer analysis of super-enhancer-induced LINC00862 and validation as a SIRT1-promoting factor in cervical cancer and gastric cancer

“…SIRT1 is one of the class III histone deacetylases (HDACs) which are dysregulated in tumor progression [ 49 ]. SIRT1 is a potential new target for gastric cancer [ 50 , 51 ]. Several non-coding RNAs interacting with SIRT1 have been identified [ 52 ].…”

Aging‐related histone modification changes in brain function

“…HDACs remove the acetyl group from ε‐N‐acetyl lysine residues of histone proteins. Based on phylogenetic comparison with yeast homologs, 18 HDACs have been identified in higher mammals and categorized into classes I, II, III, and IV 7 . Class I includes HDAC1, 2, 3, and 8, which are expressed ubiquitously and localized mainly in the nucleus.…”

“…Based on phylogenetic comparison with yeast homologs, 18 HDACs have been identified in higher mammals and categorized into classes I, II, III, and IV. 7 Class I includes HDAC1, 2, 3, and 8, which are expressed ubiquitously and localized mainly in the nucleus. Class II HDACs are further subdivided into two subgroups, with Class IIa consisting of HDAC4, 5, 7, and 9, whereas HDAC6 and 10 belong to Class IIb.…”

Design, synthesis and antiproliferative evaluation of tetrahydro-β-carboline histone deacetylase inhibitors bearing an aliphatic chain linker

“…1,2 Histone deacetylases (HDACs), which control the acetylation levels of nuclear proteins and cytoplasmic proteins, have attracted wide attention for their crucial roles in the genesis and development of neoplasms. [3][4][5] The 11 classical zinc-dependent isoforms of mammalian HDAC are divided into four categories: class I (HDAC1, HDAC2, HDAC3, HDAC8), class IIa (HDAC4, 5, 7, 9), class IIb (HDAC6, 10), and class IV (HDAC11). 6,7 Class I HDACs, especially HDAC1, are important regulators of cell proliferation and a key oncology target.…”