NCI renewal grant to develop new cancer...( Richmond Va. (Dec. 4 2007) – A Virgi...)

Richmond, Va. (Dec. 4, 2007) – A Virginia Commonwealth University Massey Cancer Center research team has received a renewal grant totaling nearly $1.3 million from the National Cancer Institute to improve the activity of a novel class of agents, known as histone deacetylase inhibitors, in the treatment of leukemia and other blood malignancies.

Through the five-year grant, Steven Grant, M.D., Massey's associate director for translational research and co-leader of the cancer center's cancer cell biology program, and his research team will focus efforts to support ongoing basic and clinical research.

Histone deacetylase inhibitors represent a diverse group of agents that modify the structure of chromatin, and by extension, genes involved in the control of death and differentiation in cancer cells. Chromatin houses the genome and is composed of DNA and scaffolding proteins, notably histones.

However, histone deacetylase inhibitors acetylate other proteins and exert multiple other effects which trigger apoptosis, or programmed cell death, in tumor cells. Acetylation is a chemical reaction that can change the molecular properties of certain proteins.

"Histone deacetylase inhibitors are currently the focus of intense interest as so-called ‘epigenetic agents,' that is, agents that act by modulating gene expression," said Grant, who is also the primary investigator for the project.

"Our goal is to exploit recent insights into the mode of action of these agents to make them even more effective in various hematologic malignancies by rationally combining them with other molecularly targeted agents," he said.

Recently, histone deacetylase inhibitors have been approved for the treatment of patients with cutaneous T cell lymphoma, a type of cancer of the immune system. In previous work, Grant's team has shown that histone deacetylase inhibitors induce acetylation and activation of a transcription factor, NF-kappaB, which
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