CancerQuest | Histone Deacetylase (HDAC) Inhibitors

HDAC inhibitors have been shown to alter the growth of several different forms of cancer.⁽¹⁾ These molecules, many of which have been isolated from natural sources, have demonstrated the ability to inhibit proliferation, induce differentiation, and cause apoptosis in tumor cells.

One exciting feature of these molecules is that they have demonstrated little toxicity in preliminary tests. Although much of the testing for these potential therapies has been performed only in cell culture and animal models, the results of these tests have been very promising and several clinical trials are underway as a result. HDAC inhibitors have been shown to affect many different types of solid and hematological cancers in research studies, including neuroblastoma, melanoma, leukemia (including APL and myeloid), breast cancer, prostate cancer, lung cancer, ovarian cancer, and colon cancer.⁽¹⁾

HDAC inhibitors are grouped into categories based on their chemical structures. The exact mechanism through which these compounds work is still poorly understood, but is a focus of current research. It is thought, though, that each inhibitor acts to inhibit a specific HDAC; this in turn has a specific effect upon gene expression, cell cycle regulation, proliferation, differentiation, and apoptosis. Scientists also believe that HDAC inhibitors cause changes in the cytoskeleton, which further aids in their anti-tumor activity. Many of these compounds are effective in very low doses and appear to act upon specific regions of the genome, altering the transcription of only select sets of genes. The true efficacy of HDAC inhibitors is yet to be determined, in testing they have shown the potential to be effective, selective treatments for some forms of cancer. These compounds may be used in combination with other anti-cancer agents.⁽¹⁾

The FDA recently approved a new HDAC inhibitor in 2006 called Vorinostat (Zolinza®)