Snapshot of new drug marks a major advance by Memorial Sloan-Kettering researchers

NEW YORK, September 9, 1999 - Memorial Sloan-Kettering Cancer Center (MSKCC) scientists have achieved a major milestone in a line of research that has spanned a quarter-century: the first-ever molecular "snapshot" of a new drug interacting with its cellular target. The picture shows how a novel cytodifferentiation agent, discovered by MSKCC researchers, closely fits into an enzyme and affects how it regulates cells. By visualizing how the drug, called SAHA, nestles into the active site of the enzyme and subtly alters its structure, the picture will enable investigators to make more potent and more specifically targeted versions of these drugs. The first clinical trial of SAHA is planned to begin this fall at Memorial Sloan-Kettering in patients with advanced cancers. Studies at MSKCC in laboratory models suggest that SAHA may have a broad role in treating cancers of the breast, lung, prostate, and other organs.

The work, published in the September 9th issue of the journal Nature, identifies the structure of the molecular target of these cytodifferentiation agents, chemical agents which can induce cancer cells to mature and die like normal cells. The concept of cytodifferentiation therapy as an approach to treating cancer has been pioneered by Center President Dr. Paul A. Marks, Sloan-Kettering Institute Chairman Dr. Richard A. Rifkind, Dr. Ronald Breslow of Columbia University, and their colleagues.

The work with SAHA holds the potential for applying cytodifferentiation agents across a broad range of cancers. The identification of the molecular target of such drugs provides a more detailed understanding of how cancer develops and suggests more specific ways to interfere with that process. "It's a new therapeutic approach to cancer," Dr. Marks said.

What exactly does histone deacetylase do in cells, and how does SAHA interfere with it? Histones are proteins in the nuclei of cells; the histones provide a core around which the long chains of DNA

Contact: Christine Westerman
Memorial Sloan-Kettering Cancer Center

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