Targeting Cancer's Sweet Tooth
An ideal cancer therapy would be specific in targeting cancer cells over normal tissues, yet not be exclusive to one type or stage of cancer. This is the basic idea behind many of the traditional chemotherapies that target the cancer-cell characteristic of rapid cell division. The problem there is that many normal tissue types, such as the cells of the gastrointestinal tract, hair follicles, skin, and bone marrow, are also rapidly diving and thus negatively affected by these therapies.
In recent years, many oncology researchers have been turning their attention to a different aspect of cancer cell biology – the cells’ extremely high use of glucose. Cancer cells are referred to as “highly glycolytic” in that they consume glucose at a rate as much as 200 times higher than that of normal cells. This metabolic abnormality can be exploited as a therapeutic target.
In the January 1 2012 issue of Cancer Research, investigators from the Kyushu University Medical School and the University of California, San Diego published a report demonstrating promising results in animal models of cancer by treating the animals with a glucose analogue that helps to activate cells death. The glucose analogue, known as 2-deoxyglucose or 2-DG, is readily taken up by cancer cells but cannot be converted to energy. Instead, 2-DG primes the cells for death, by breaking up a three-protein complex, exposing a critical protein switch for programmed cell death or apoptosis. After this priming step, the animals received a second drug, ABT-263, that flips the exposed switch, turning on apoptosis. Brain cells are also highly glycolytic, but the second drug, ABT-263, cannot cross the blood-brain barrier, thus protecting brain cells and making cancerous cells the primary target for this potential new drug combination. The treatment has shown positive results in a variety of animal models of different cancers, including leukemia, liver, lung, breast and cervical cancers, as well as a chemo-resistant, metastasized version of prostate cancer.
The next step, of course, is human clinical trials. Both 2-DG and ABT-263 are already in Phase 2 trials for other indications, indicating that there is already significant safety data on each. If the drug combination proves to be safe and effective in human cancer patients, it may open the door to a new type of targeted treatments for a whole range of cancers.
Labels: cancer research, highly glycolytic cells, targeting cancer

