A drug that has served as a mainstay treatment for children with leukemia since the 1970s now shows the unexpected and beneficial effect of preventing breast cancer spread to bone — one of the most feared and common problems for women with advanced breast cancer. The new finding, from The University of Texas Health Science Center at San Antonio (UTHSCSA) and OsteoScreen Ltd., is reported in the Nov. 18 issue of the Journal of Clinical Investigation.
"Metastasis (cancer spread) into bone from the breast is almost invariable in women who have advanced disease," said senior author Gregory Mundy, M.D., professor of cellular and structural biology at UTHSCSA, assistant dean for clinical research in the UTHSCSA School of Medicine, and president and chief executive officer of San Antonio-based OsteoScreen. "The bone contains a tremendous reservoir of nutrients that allow cancer to grow, and the bulk of the tumor is likely to be in the bone."
The drug is called 6-Thioguanine (6-TG). Dr. Mundy and his colleagues were screening thousands of drugs, including 6-TG, for inhibitory action against breast cancer metastasis. Although they hit pay dirt with 6-TG, Dr. Mundy cautioned that the studies were conducted in mice and that the findings must be confirmed in human trials.
The same group made a similar discovery two years ago when it was announced that the statins, a class of drugs for regulating cholesterol, are effective in promoting bone formation. That finding holds promise for treatment of the bone-thinning disease osteoporosis. "In both cases we were searching for drugs to treat serious conditions, and came across old drugs with new potential uses," Dr. Mundy said.
Bone cancer patients suffer terrible complications including pain, fractures and deformities. "We've found that 6-TG reduces the bone complications but also the amount of tumor in bone," Dr. Mundy said. "This is important because some women can live for many years with bone metastasis, and what we're trying to do here is make it more benign."
The experiments lasted four weeks. The researchers studied 6-TG's effect on mice in which human tumor cells had metastasized to bone. The five mice that received no treatment died quickly, but four of the five mice treated with 6-TG were still alive after four weeks.
"The compound changes the microenvironment in the bone, making it a less-favorable place for the tumor to grow," Dr. Mundy said. "It's like the old seed and soil hypothesis. We're not affecting the seed, which is the tumor cell, but the soil. 6-TG blocks the tumor's capacity to produce a tumor peptide called PTHRP, or parathyroid hormone-related peptide. In turn, this decreases the tumor's capability to destroy bone. This is the scientific rationale behind our finding."
Dr. Mundy said the next step is to reproduce the results in people. "We have a study planned for patients with advanced breast cancer. We hope we can administer this drug in lower doses than it is used in treatment of leukemia," he said. "Our goal is for the women to have less pain and live longer."
Co-authors are Theresa Guise, M.D., formerly of UTHSCSA and now with The University of Virginia, and Wolf Gallwitz, Ph.D., senior scientist at OsteoScreen.