Concept of histone deacetylases in cancer: Reflections on esophageal carcinogenesis and treatment.
Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type worldwide, though, a continuous increase in esophageal adenocarcinomas has been noted in the past decades. Common risk factors associated with EC include smoking, alcohol consumption, gastroesophageal reflux disease, Barrett's esophagus and obesity. In an effort to overcome chemotherapy resistance in oncology, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Based on this knowledge, histone acetylation was addressed as a potential novel chemotherapy drug target to repress cancer cell proliferation. There are four classes of histone deacetylases (HDACs) inhibitors with a variety of different mechanisms of actions that render them possible anti-cancer drugs. They arrest the cell cycle, inhibit differentiation and angiogenesis and induce apoptosis. They do not necessarily act on histone proteins, since they can also exert indirect anti-cancer effects, by modifying various cellular proteins. In addition, HDACs have also been associated with increased chemotherapy resistance. Based on the literature, HDACs have been associated with EC, with surveys revealing that increased expression of certain HDACs correlates with advanced TNM stages, tumor grade, metastatic potential and decreased 5-year overall and disease-free survival. The aim of this survey is to elucidate the molecular identity and mechanism of action of HDAC inhibitors as well as verify their potential utility as anti-cancer agents in esophageal cancer.
Schizas, D; Mastoraki, A; Naar, L; Spartalis, E; Tsilimigras, DI; Karachaliou, G-S; Bagias, G; Moris, D
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