WASHINGTON, Aug. 30 -- A non-toxic chemical compound that prevents cancer cells from producing a critical membrane component has been shown to suppress tumor growth and tumor size in mice without unwanted side effects, according to researchers at the Children's National Medical Center in Washington, D.C. The finding could lead to the development of safe and effective human cancer treatments that do not have the harsh side effects associated with chemotherapy and other traditional cancer-fighting strategies.
The compound, a carbohydrate known as OGT2378, blocks the production of an enzyme that cancer cells need to make gangliosides, molecules found in the membranes of most cells. When secreted by cancer cells, gangliosides suppress the immune system, alter the microenvironment surrounding these cells and promote the growth of new blood vessels necessary for tumor growth and survival.
"Cancer cells produce gangliosides at a much more rapid rate than normal cells. By interfering with this process we can stop a tumor from growing in a rather dramatic fashion without damaging the normal tissue surrounding it," says Stephan Ladisch, M.D., director of the Center for Cancer and Immunology Research at the Children's Research Institute. His findings were presented today at the 230th national meeting of the American Chemical Society, the world's largest scientific society.
Tumors in mice treated with OGT2378 were one-tenth the size of those in untreated mice. The results suggest that a drug or other treatment can modify tumors in such a way that the body's own defenses are able to attack the cancerous cells and eliminate growth, apparently without harmful side effects, Ladisch says.
"Chemotherapy and radiation are limited by the fact that the body can only withstand so much toxic exposure," Ladisch says. "As far as we know that's not the case with these inhibitors of ganglioside production."
Although this approach doesn't kill tumors, it makes them potentially easier to treat in other ways, Ladisch says. In some instances, the treatment might prevent cancer from recurring. In other cases, ganglioside inhibitors could be used in combination with chemotherapy to treat cancers that do not respond to chemotherapy alone. However, additional studies are needed to confirm that this approach is safe and effective in animals. It may still be several years before human clinical trials are conducted, Ladisch says.
In his studies, Ladisch found that 15 mice given OGT2378 as a dietary supplement beginning three days before being implanted with melanoma cells had significantly smaller tumors (61 millimeters in volume) a month after exposure compared to 15 untreated mice (538 millimeters in volume). Tumor growth also was significantly arrested in mice implanted with melanoma cells that were pretreated with OGT2378 as a way to reduce ganglioside production. In another study, mice treated with the compound seven days after being exposed to melanoma cells developed smaller tumors (101 millimeters in volume) over the next 31 days than untreated mice (620 millimeters in volume).
"The absence of these gangliosides allows the body to more easily curb tumor growth," Ladisch says. "While we don't yet know the mechanism of the effect, what we do know is that we are changing the tumor's own mechanics to stop its growth."
The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 158,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.
-- Doug Dollemore
The paper on this research, CARB 44, will be presented at 3:50 p.m., Tuesday, Aug. 30, at the Convention Center, Room 202A, during the "Iminosugars: Therapeutic Potential" symposium.
Stephan Ladisch, M.D., is scientific director of the Children's Research Institute and a professor of Pediatrics and of Biochemistry/Molecular Biology at the George Washington University School of Medicine in Washington, D.C.