Dartmouth researchers may have found a way to stop breast cancer tumors from growing, which would make the cancer easier to treat. The findings are the result of experiments conducted on mice by Dartmouth Medical School professor William North and his team.
North's experiments explore the effectiveness of blocking the activation of NMDA receptors, on the surface of the breast cancer cells to block them from multiplying. North discussed the results of his study, which began in 1994, in a lecture at Dartmouth-Hitchcock Medical Center Wednesday.
NMDA receptors are members of a protein group that sits on the surface of cells and, when activated, assists in cell proliferation. NMDA receptors are important in nerve cells within the brain for controlling learning and memory, but when they are located on cancer cells, they promote the growth of cancerous tumors.
North and his colleagues implanted human breast cancer cells and estrogen -- which promotes cancer growth -- in mice to test the effects of blocking the NMDA receptors. After the tumors reached 0.5 to 2 centimeters, the scientists treated them with small dosages of antagonist MK801 twice a day. Antagonists block activation of the NMDA receptors by filling the niche on the protein that is normally occupied by the activator.
Their results showed that treating the mice with the MK801 almost immediately inhibited cancer growth.
"What we found in these studies so far is if we can block these proteins from being activated, we can decrease the growth of these cancer cells," North said. "What we would hope then is that this might translate over eventually to some form of patient care."
A possible problem with using antagonists such as MK801 to block activation of the NMDA receptors is that the antagonists may travel into the brain and negatively affect cell function there, North said. There was no noticeable weight or behavioral difference between the control mice and the mice treated with the antagonist because of the small dosage that they used, which suggests that the antagonists did not affect brain function.
"The mice grew well and didn't seem to have any problems, so the level of material we gave them didn't seem to affect them in a bad way," he said.
Antibodies -- large molecules that have been shown to block activation of receptor proteins in lung and other cancer cells -- do not travel to the brain and may thus be a safer way of blocking tumor growth in humans, according to North.
"We have done other studies with antibodies, not with breast cancer but with another type of cancer," he said. "We've found that antibodies can have the same affects as these small antagonists."
In the United States, approximately 200,000 people per year fall victim to breast cancer, North said. He distinguished between high-grade and low-grade breast cancer. The five-year survival rating for patients suffering with low-grade breast cancer is roughly 100 percent, while the more invasive high-grade breast cancers involve larger tumors, which make the cancer harder to treat. North hopes his research will be able to assist patients suffering from high-grade cases, he said, but it is too early to tell whether that will be possible.
"Very often in research you get very positive and encouraging results, and when you turn to the patient you don't see these being borne out," he said. "But we've found that the research we've done so far in this area is very encouraging."
In addition to teaching physiology at DMS, North is the director of Dartmouth's Protein Analysis Unit and the DMS Endocrine Training Program, a fellowship program for medical students.
