Histone deacetylases are enzymes involved in the modification of histones in order to allow DNA to wrap around them tightly. The enzymes achieve this through removal of the acetyl group from the lysine amino acid on a histone. This process is important because it determines how DNA is wrapped around histones and acetylation and deacetylation regulate DNA expression.
Histone deacetylases and histone acetyltransferases work in opposition to ensure that gene expression is regulated throughout chromatin remodelling. Altered expression or mutation in the genes that code for these enzymes is a key contributor to the onset of cancer.
Histone deacetylase inhibitors are specific targeted anti-cancer drugs that can reactivate gene expression and inhibit the histone deacetylases that aid cancer cell proliferation, growth and survival. In 2006, a histone deacetylase inhibitor called vorinostat was approved by the Food and Drug Administration for the treatment of cutaneous T-cell lymphoma.
Histone deacetylase inhibitors can selectively change around 2% to 10% of the expressed genes within the cancer cells. In multiple myeloma, vorinostat acts on the ARP-1 cell line in the following ways:
Suppresses the genes of the insulin like growth factor/insulin-like growth factor-I receptor
Suppresses interleukin-6 receptor signalling cascades that promote plasma cell growth and proliferation
Suppresses anti-apoptotic factors such as caspase inhibitors and oncogenic kinases that prevent programmed cell death or apoptosis.
Suppresses the DNA synthesis and repair enzymes in cancer cells that would otherwise prolong their survival
Histone deacetylase inhibitors may also be used in combination with other cancer treatments such as radiation therapy, chemotherapy, epigenetic therapy and other biological and targeted therapies.