ENZYMES: Enzyme Is Target for Cancer Drug - Brief Article

Applied Genetics News,  Jan, 2000  

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New York University (NYU) School of Medicine and Pharmacia & Upjohn (P&U, 95 Corporate Dr., Bridgewater, NJ 08807; Tel: 908/768-5501, Fax: 908/306-4433) have entered into a multi-year research and license agreement to collaborate on the development of a key enzyme, prenylcysteine carboxyl methyltransferase (pcCMT), as a target for anti-cancer drug discovery. Under the agreement with NYU, Pharmacia & Upjohn has obtained an exclusive worldwide license to the technology with the right to sublicense and commercialize resulting products.

PcCMT is one of four enzymes required for the maturation of the product of the ras oncogene. Mutations of ras are implicated in many forms of cancer. Ras proteins are located in the cell's outer membrane where they help conduct signals for cellular growth from the external environment to the cell's nucleus. Mutated forms of ras are thought to continually stimulate cell division, giving rise to tumors.

"Ras is a molecular switch stuck in the 'on' position in cancer," explains Mark R. Philips, associate professor of medicine and cell biology at NYU. "No one has been able to figure out how to turn it off." Philips developed the technology on which the NYU/P&U collaboration will be based.

The roll of pcCMT in regulating interactions of ras-like proteins was described by Philips in a 1993 paper in the journal Science. Later, he identified and cloned the gene that encodes the human enzyme. Earlier this year, Philips published, in the journal Cell, the results of a study showing that ras molecules destined for the surface membrane first visit internal membranes of the cell where they encounter pcCMT, a step required for further transport of the molecules to the cell's surface.

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