"Exisulind and other SAANDs appear to act at an early point in the biochemical pathway that controls apoptosis and survival of cancer cells," said W. Joseph Thompson, Ph.D., vice president of research at Cell Pathways and lead author of the publication. "Our initial data indicates that increased PDE5 expression, and in some cases PDE2, occurs in precancerous and cancerous lesions. This over-expression appears to keep cGMP low in cells that have abnormal proliferation or apoptosis rates. The data indicate that by inhibiting cGMP PDE activity in cancer cells, a sustained rise in cGMP occurs, triggering cell death through protein kinase G. In normal cells, the cGMP pathway does not appear to be important in the regulation of apoptosis. Exisulind and other SAANDs restore the ability of abnormal cells to die by inhibiting that cGMP PDE activity."
New Insights in the Biology of Cancer
Cyclic nucleotide PDEs consist of 11 gene families, each having one or more different members or "isoforms." Each family of PDEs is characterized by their ability to bind and degrade cyclic AMP (cAMP) and/or cGMP, but differs in their immunological, physical and kinetic properties. Only a limited number of PDE isoforms are expressed and used by any single type of cell or tissue to regulate cGMP or cAMP levels. Pharmaceutical developers have been studying these enzymes as potential drug targets to modulated cyclic nucleotide levels in diseases where their levels are important, such as asthma and heart disease. Until now, PDE inhibitors have not been developed as anti-cancer agents. Mo
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