UM/Sylvester Scientist Devises Way to Target Slow-Growing Cancer Cells
The University of Miami Sylvester Comprehensive Cancer Center has opened a Phase I clinical trial on a potential treatment for slow-growing tumor cells. The treatment has shown great promise in a variety of solid tumors in the laboratory and would be the first of its kind to focus on these hard-to-treat cancer cells, which can also contribute to metastasis. Theodore J. Lampidis, Ph.D., a scientist in the Tumor Cell Biology Program at UM/Sylvester, developed a way to target these slow-growing malignant cells through glycolysis, the process by which a cell converts sugar into energy.
The human body is made up mostly of cells that divide slowly, although cells in hair, the GI tract, and bone marrow grow quickly. Standard chemotherapy attacks all fast-dividing cells in the body regardless of whether they are normal or cancerous – that’s why patients receiving chemotherapy lose their hair and have lower white blood cell counts. It is also why slow-growing tumor cells are the most difficult to cure. One of the main reasons standard chemotherapy does not always work completely is because the slow growing cells are not targeted by this treatment. They survive and give rise to more rapidly dividing tumor cells that eventually become resistant to all drugs.
Tumor cells grow slowly if they can’t get an adequate blood supply. Dr. Lampidis reasoned that since slow-growing tumor cells are in a microenvironment of low oxygen (hypoxia) because of their low blood supply, they metabolize sugar much less efficiently than when they are in a normal oxygen environment. Under hypoxia these tumor cells need to take up much more sugar to survive than normal cells in the body which are well-oxygenated. This creates a window of opportunity between slow-growing tumor cells and slow-growing normal cells that can be exploited. Because the hypoxic tumor cells aggressively take in more sugar if they are fed false sugars such as 2-deoxyglucose (2-DG) their only energy source is cut off and they literally starve to death.
Normal cells can withstand this treatment for two reasons. First, they take up less of this false sugar than tumor cells do. Second, because they are exposed to oxygen through normal blood flow, normal cells can also utilize fats and proteins as alternative sources of energy. In contrast the slow-growing tumor cells, due to their lack of oxygen, cannot metabolize fats or proteins and therefore when their sugar metabolism is blocked with the 2-DG treatment, they die.
Dr. Lampidis has worked in conjunction with Threshold Pharmaceuticals in San Francisco, California, to test his hypotheses in animal models. He and his colleagues recently reported in Cancer Research, January 1, 2004, their success against human tumors growing in animal models by demonstrating that when 2-DG is added to standard chemotherapy it significantly increases the effectiveness of treatment. View the publication at this link: http://cancerres.aacrjournals.org/cgi/content/abstract/64/1/31.
The Phase I clinical trial, which is primarily designed to confirm 2-DG’s safety and determine the maximum tolerable dose, is now open to UM/Sylvester patients diagnosed with a variety of solid tumors. “We hope to augment the conventional tumor response we see with chemotherapy and radiation therapy, reproducing Dr. Lampidis’ experiments in the lab,” said Luis Raez, M.D., who will lead the Threshold-sponsored clinical trial. Dr. Raez specializes in lung and head and neck tumors, but will enroll patients with a variety of metastatic cancers in the study. He plans to enroll 30 patients over the next two years.
2-DG is orally administered – it is a clear liquid developed by Threshold that the patient drinks like water. 2-DG by itself is not expected to produce chemo-related side effects because it only targets slow-growing cancer cells. But to attack both slow and fast-growing cancers it is given together with standard chemotherapy, Taxotere docetaxel, so patients in the trial may undergo hair loss and other symptoms associated with conventional treatment. For more information about this clinical trial or UM/Sylvester, please call (800) 545-2292 or (305) 243-1000.
UM/Sylvester was founded in 1992 to provide comprehensive cancer services and today serves as the hub for cancer-related research, diagnosis, and treatment at the University of Miami School of Medicine. UM/Sylvester handles more than 1,100 inpatient admissions annually, performs 2,800 surgical procedures, and treats 2,900 new cancer patients. All UM/Sylvester physicians are on the faculty of the University of Miami School of Medicine, South Florida’s only academic medical center. In addition, UM/Sylvester physicians and scientists are engaged in 150 clinical trials and receive more than $30 million annually in research grants. UM/Sylvester at Deerfield Beach recently opened to better meet the needs of residents of Broward and Palm Beach Counties. This 10,000 square-foot facility at I-95 and S.W. 10th Street offers appointments with physicians from six cancer specialties, complementary therapies from the Courtelis Center, and education and outreach events.