VCU news

By Lorraine Cichowski and David Gewirtz

RICHMOND, Va. – Researchers at Virginia Commonwealth University Medical Center have found that a form of Vitamin D given before low-dose radiation to treat breast cancer significantly enhanced the ability of irradiation to kill malignant cells without damaging healthy tissue.

The study, to be published in the May print edition of Cancer Chemotherapy and Pharmacology and available online now, also suggests that combining the Vitamin D compound and low-dose radiation results in continued death of breast cancer cells for a week after treatment and may inhibit recurrence. The results could lead to shorter radiation treatment periods for breast cancer patients and could present new treatment options for other cancers that are resistant to radiation.

“Many of the current chemotherapy regimens used to treat breast cancer are quite toxic,” says David A. Gewirtz, Ph.D., and professor of pharmacology and toxicology at VCU. “There has been a great deal of interest in the scientific community in developing drug treatments that will have limited toxicity to the patient. We’ve been looking at Vitamin D and Vitamin D analogs because they appear to have the capacity to interfere with growth of breast tumor cells and, under the right experimental conditions, to promote cell death.

“Our study shows that pre-treatment of breast tumor cells with a Vitamin D analog significantly enhanced the effectiveness of the irradiation treatment.”

Each year approximately 200,000 women in the United States are diagnosed with breast cancer.  Of that number, about 40,000 die from the disease, making breast cancer the leading cause of cancer deaths among women between the ages of 20 and 59. Radiotherapy is commonly used to treat breast cancer, both before surgery to reduce the size of tumors and after surgery to reduce recurrence of tumors, sometimes in combination with chemotherapy.

There has been increasing evidence that Vitamin D – which is naturally manufactured by the body after exposure to sunlight – helps to prevent and treat several forms of cancer. But too much Vitamin D can cause the body to absorb excessive calcium into the blood and be toxic to the patient. Scientists have modified Vitamin D to create less-toxic “analogs,” including the Vitamin D compound ILX 23-7553 tested in Gewirtz’s lab for this study.

The VCU researchers used breast cancer cell cultures to test the effect of ILX 23-7553 alone and in combination with low doses of ionizing radiation in killing cancer cells. They found that pre-treating the cells with the Vitamin D compound before radiation reduced the number of cancer cells after irradiation by almost 30 percent more than radiation treatment alone.  Subsequent tests on healthy cells revealed that the Vitamin D/radiation treatment had no adverse effect on healthy cell tissue.

The combination of ILX 23-7553 and irradiation caused breast cancer cells to continue to die seven days after treatment, while no cell death was observed at that time when cells were treated only with irradiation. The combination was three times more effective than radiation alone in preventing resumption of tumor cell growth.

“These results suggest that Vitamin D analogs such as ILX 23-7553 may one day prove to have utility in combination with conventional radiotherapy of breast cancer as well as other malignancies such as prostate cancer and very aggressive forms of brain cancer that may be more resistant to radiation,” Gewirtz said.

Previous studies by Gewirtz’s lab have found that Vitamin D compounds enhance chemotherapy and single, high-dose radiation treatments for breast tumor cells.

Although the Vitamin D analogs are undergoing clinical trails, none has been approved yet for use in human cancer patients.