Histone Deacetylases and their Inhibitors in Colorectal Cancer Therapy: Current Evidence and Future Considerations

Abstract

: Colorectal cancer (CRC) comprises a heterogeneous group of gastrointestinal tract tumors. It is a multifactorial disease, and a plethora of distinct factors are involved in its pathogenesis and pathophysiology. The development of CRC is not limited to genetic changes, but epigenetic and environmental factors are also involved. Among the epigenetic factors, histone deacetylases (HDACs), a group of epigenetic enzymes that regulate gene expression, have been reported to be over-expressed in CRC. HDACs and their inhibitors seem to play an important role in the molecular pathophysiology of CRC. The aim of this review was to define the role of HDAC inhibitors as potential anticancer agents against CRC.

Clinical Significance of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer

“…As aforementioned, HDACs are currently regarded as crucial factors in the regulation of the cell cycle, including cell differentiation, apoptosis, and proliferation, in different types of cancer [ 15 , 25 , 41 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Their over-expression correlates with the management and survival of the patient.…”

“…During the last three decades, great progress on the pathophysiology of BC has been achieved through extensive research, leading to the development of possible novel therapeutic approaches. In addition, a variety of human malignancies, such as lung, colorectal, gastric, thyroid, prostate, endometrial, hepatocellular, kidney, pancreatic, melanoma (including uveal), breast, and hematological malignancies, over-express HDACs [ 15 , 25 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The majority of these studies have highlighted the correlation between HDAC over-expression and parameters such as the histological grade, the stage of the tumor, and the survival of the patients.…”

Role of histone deacetylase inhibitors in diabetic cardiomyopathy in experimental models (Review)

“…of note, four of them have already been approved by the US Food and Drug administration (FDa) against hematological malignancies (14). additionally, their anticancer activity has been reported extensively in the literature, including colorectal, hepatocellular, pancreatic, breast, thyroid, lung, endometrial, and other cancers such as uveal and cutaneous melanoma (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Furthermore, their role appear to be crucial in fighting other diseases, including viral infections and both inflammatory and neurological disorders (28,29).…”

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy

“…These post-translational acetylations are regulated by the rival effects of histone acetylases (HATs) and histone deacetylases (HDACs) [ 17 , 18 , 19 , 20 ] ( Figure 1 ). Of note, HDACs catalyze the removal of acetyl groups on the NH2-terminal lysine residues, thereby repressing transcription and tumor-suppressor gene activation [ 21 , 22 , 23 , 24 ]. As a consequence, the deregulation of histone acetylation potentially justifies the genesis of diverse human cancer entities [ 25 , 26 , 27 ].…”