Histone Deacetylase Functions in Gastric Cancer: Therapeutic Target?

SIMPLE SUMMARY: Our knowledge about the identity of many cancers has increased greatly during the last years and progress in their early identification as well as treatment options led to a net increase in the survival of many cancer patients. Unfortunately, gastric cancer does not belong to these cancers as it is still very badly treated and the chances to survive it are very low, less than 25%. This is mainly due to the fact that currently there are no possibilities to detect it at early stages and that tumors of gastric cancer patients seem all to be more or less different. In this respect, our knowledge about the differences between the gastric cancer from one patient to another is very limited. However, one family of proteins called “Histone Deacetylases” or HDACs, in contrast, seem to be present or their function altered in gastric cancers. This review summarizes our current knowledge about their role in gastric cancer development and their potential as an early detection marker and target to develop new treatment options. 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.