Cancers are usually an outcome of the alternations in the genetic material. Genetic and epigenetic changes regulate the alternations in the DNA. The genetic events include rearrangement of chromosomes, amplification of genetic material, mutations within DNA etc. These events influence the expression of tumor suppressor genes. They stimulate the expression of the products of proto-oncogenes. Epigenetic changes however influence the expression of genes in a mutation independent manner. These influences can be effectively controlled by the inhibitors of histone deacetylases. Belinostat is one such inhibitor which can be administered alone or in combination with other inhibitors.

Belinostat targets the reversal of the silencing of the suppressor genes (which suppress the tumors) by epigenetic mechanism. The two main epigenetic mechanisms which regulate the gene expression include histone modifications and methylation of DNA. When the CpG islands within the promoter regions over methylated, the access to the transcriptional factors is blocked. This leads to the silencing of the genes which are involved in the process of suppression of tumors [1]. Histone deacetylases stimulate the hypoacetylation and hence suppression of the genes. Belinostat is a newly discovered inhibitor which is derived from hydroxamate group of compounds. It inhibits the activity of HDACs at a low concentration (nanomolar concentrations). It stimulates the acetylation of histone proteins and hence checks the growth of the tumor cells. Preclinical studies were done to study its effect singly or in combination with other inhibitors like carboplatin, paclitaxel and docetaxel on different cancer types. It was highly effective against ovarian cancer under both in vitro and in vivo conditions. It was also effective against the tumor cells which were resistant to multiple inhibitors. Belinostat effectively curbed the growth of human xenograft model and its activity was further stimulated when it was administered along with carboplatin. The α-tubulin was acetylated in the presence of docetaxel and H2AX was phosphorylated under in influence of carboplatin. These two effects were further enhanced in the presence of Belinostat [2].

The inhibitor Belinostat is well tolerated under in vivo conditions and can efficiently check the growth of lymphoma related to the T – cells. It checks the melanoma which occurs again and again and which is resistant to different kinds of therapies. It is efficient in both peripheral and cutaneous T-cell lymphomas [3].

Among the different HDAC inhibitors, PXD101 and Romidepsin are very effective in stimulating the cell death through various mechanisms within the melanoma cells. They arrest the cell cycle of the cancer cells and stimulate the synthesis of the death receptors which lead to the death of the cancerous cells. In some cases they also promote the differentiation of the cancerous cells. In case of lymphoma caused within mantle cells (MCL), translocation of a fragment of chromosome (t(11;14)(q13;q32)) takes place This stimulates the expression of cyclin D1 protein. Bortezomib is an inhibitor of proteasome and when it was combined with the inhibitors of HDACs, an increased membrane depolarization was noticed. This also stimulated the process of apoptosis within PBMCs. This combination acetylated the proteins like α-tubulin, histone H3 and Noxa and decreased the levels of Bcl-X_L and cyclin D1 within the cancerous cells.

In a nut shell, Belinostat controls HDACs and hence checks the growth of cancers in an effective manner. It has shown effective results when administered alone or in combination with other inhibitors of HDACs.