Combining a new drug target with an interventional radiology technique using ultrasound-guided injection of the drug directly into the tumor, reduced breast tumors in mice by as much as 90 percent and delayed metastasis, say researchers.
Study co-author Dr. Jeff H. Geschwind, director of vascular and interventional radiology at Johns Hopkins University School of Medicine, says the researchers used a new drug target for cancer cells. The drug, called 3-BrPA, blocks glycolysis, the process by which breast cancer cells generate adenosine triphosphate (ATP). ATP transports chemical energy within the cells, which is essential for growth. The researchers combined this drug with a minimally invasive administration using ultrasound to guide a needle into the tumor, thus reducing exposure of healthy cells to the drug.
While the study was performed in mice, Geschwind envisions the minimally invasive breast cancer treatment could be performed in humans on an outpatient basis. “The treatment would likely just require every other day infusion of the drug 4 or 5 times to achieve complete tumor kill,” Geschwind told The Hub by e-mail. “One infusion may even be enough provided the tumor is small enough.”
The study was presented today at the Society of Interventional Radiology annual meeting in Chicago. Background material in the abstract explained that, in contrast to normal cells that use oxidative phopshorylation to generate ATP, cancer cells use glycolysis. The drug 3-BrPA is an anti-glycolytic agent, which Greschwind says they have also used in liver, brain and pancreatic tumors.
In the study, the researchers assessed the ability of 3-BrPA to reduce ATP in cell cultures in the laboratory. They found dose-dependent decreases in ATP, demonstrating that the cancer cells were sensitive to the drug. They then used the drug in a mouse model, injecting it into three groups of five mice. One group received a low dose of 3-BrPA, one group received a higher dose and the third group received a saline solution as a control group.
Using ultrasound imaging to precisely guide the needle to the tumors, researchers performed the treatments every other day for two weeks. Tumor size was measured using ultrasound. On day six, there was a statistically significant lower tumor volume in the high-dose group compared to the control group. Statistically significant lower volume of tumor was seen on day 12 in the low-dose tumor group compared to the control group.
After two weeks, tumors treated with the low-dose of 3-BrPA showed an average 58 percent reduction in volume compared to the control group, and the tumor volume in high-dose group had been reduced by an average of 91 percent. When they examined other tissues in the mice they found no difference in the normal tissues of the control mice and that of the treated mice, indicating low toxicity to untreated tissues.
"In our study, a statistically significant difference in tumor volume was observed,” Geschwind said. “Our results support the continuing development of this highly innovative interventional radiology approach for the safe and effective treatment of breast cancer." He noted, however, that it will require additional studies before they apply for human clinical trials. "Before we can test our novel treatment strategy in individuals with breast cancer, it is important to perform additional animal studies of a larger size to confirm the efficacy of the treatment and to verify that there are no toxic effects on the normal tissues," Geschwind concluded.
By Michael O'Leary, contributing writer, Health Imaging Hub