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Meanwhile, professor of pediatrics and biochemistry and molecular biology Stephan Ladisch of Children s National Medical Center and George Washington University School of Medicine, Washington, D.C., and coworkers are trying to curb tumor growth with iminosugar inhibitors of tumor ganglioside synthesis.

The synthesis and secretion of gangliosides by tumor cells has been shown to block immune responses against tumor growth and also to promote angiogenesis, the development of blood vessels to supply tumors. Therefore, inhibiting ganglioside synthesis might be an effective way to fight cancer.

Ladisch and coworkers identified an orally available iminosugar, OGT2378, that inhibits glucosylceramide synthesis, a process upon which ganglioside synthesis depends. The iminosugar has been shown to curtail melanoma growth in treated mice to one-tenth that in control mice.

"Cancer cells produce gangliosides at a much more rapid rate than do normal cells," Ladisch explained. "By interfering with this process, we can stop a tumor from growing in a rather dramatic fashion without damaging the normal tissue surrounding it."


Although Ladisch and coworkers do not yet know the precise molecular mechanism of the effect, "what we do know is that we are changing the tumor s own mechanics to stop its growth," he said. "This novel approach to treating cancers could serve either as an alternative to traditional cancer-fighting therapies with harsh side effects--such as chemotherapy and radiation treatment--or as a supplement to these standard treatments." It may still be several years, however, before human clinical trials are carried out, Ladisch said



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