The compound, acarbohydrate known as OGT2378, blocks the production of an enzyme thatcancer cells need to make gangliosides, molecules found in themembranes of most cells. When secreted by cancer cells, gangliosidessuppress the immune system, alter the microenvironment surroundingthese cells and promote the growth of new blood vessels necessary fortumor growth and survival.
"Cancer cells produce gangliosides ata much more rapid rate than normal cells. By interfering with thisprocess we can stop a tumor from growing in a rather dramatic fashionwithout damaging the normal tissue surrounding it," says StephanLadisch, M.D., director of the Center for Cancer and ImmunologyResearch at the Children’s Research Institute. His findings werepresented today at the 230th national meeting of the American ChemicalSociety, the world’s largest scientific society.
Tumors in micetreated with OGT2378 were one-tenth the size of those in untreatedmice. The results suggest that a drug or other treatment can modifytumors in such a way that the body’s own defenses are able to attackthe cancerous cells and eliminate growth, apparently without harmfulside effects, Ladisch says.
"Chemotherapy and radiation arelimited by the fact that the body can only withstand so much toxicexposure," Ladisch says. "As far as we know that’s not the case withthese inhibitors of ganglioside production."
Although thisapproach doesn’t kill tumors, it makes them potentially easier to treatin other ways, Ladisch says. In some instances, the treatment mightprevent cancer from recurring. In other cases, ganglioside inhibitorscould be used in combination with chemotherapy to treat cancers that donot respond to chemotherapy alone. However, additional studies areneeded to confirm that this approach is safe and effective in animals.It may still be several years before human clinical trials areconducted, Ladisch says.
In his studies, Ladisch found that 15mice given OGT2378 as a dietary supplement beginning three days beforebeing implanted with melanoma cells had significantly smaller tumors(61 millimeters in volume) a month after exposure compared to 15untreated mice (538 millimeters in volume). Tumor growth also wassignificantly arrested in mice implanted with melanoma cells that werepretreated with OGT2378 as a way to reduce ganglioside production. Inanother study, mice treated with the compound seven days after beingexposed to melanoma cells developed smaller tumors (101 millimeters involume) over the next 31 days than untreated mice (620 millimeters involume).
"The absence of these gangliosides allows the body tomore easily curb tumor growth," Ladisch says. "While we don’t yet knowthe mechanism of the effect, what we do know is that we are changingthe tumor’s own mechanics to stop its growth."
The AmericanChemical Society is a nonprofit organization, chartered by the U.S.Congress, with a multidisciplinary membership of more than 158,000chemists and chemical engineers. It publishes numerous scientificjournals and databases, convenes major research conferences andprovides educational, science policy and career programs in chemistry.Its main offices are in Washington, D.C., and Columbus, Ohio.
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