The researchers discovered that when an Food and Drug Administration-approved cancer treatment typically used to treat cutaneous T-cell lymphoma was administered before a novel experimental antitumor agent -- which works best in breast cancers expressing the estrogen receptor (ER) -- estrogen receptors were reinstated in receptor-negative breast cancer cells so that treatment was also effective in fighting the difficult to treat ER-negative disease.

The research was supervised by Angelika Burger, Ph.D., director of the Translational Research Laboratory at the Karmanos Cancer Institute and professor of the Department of Pharmacology at the School of Medcine. Karri Stark, a doctoral candidate with the School of Medicine, presented the findings.

Researchers have paired vorinostat, known by its pharmaceutical name Zolinza®, with Aminoflavone Prodrug (also known as AFP464) and found that AFP464 and vorinostat work together to inhibit the growth of triple-negative breast cancer cells. “Triple-negative” refers to breast cancer cells that have no estrogen, progesterone or HER2 receptors needed for currently available, targeted anticancer therapies to work effectively.

AFP464 is now in Phase I clinical trials at the Karmanos Cancer Institute, the Mayo Clinic in Minnesota, and other cancer research centers in Paris and Brussels in Europe.

Dr. Burger said the findings offer particular hope to those women battling triple-negative breast cancer.

“We could now find a way to treat every kind of invasive, metastatic breast cancer, the ER-positive and ER-negative types with AFP464,” she said. “The synergism is very impressive. We always knew vorinostat can reprogram the expression of cancer cells.”

AFP464 has been in Phase I clinical trial for the last year and a half, in which doses were given to patients with solid tumors. Dr. Burger said the next step is to take the anti-cancer agent to the second phase, where researchers administer to triple-negative breast cancer patients the drug alone or in combination with vorinostat. She expects that to occur in the next year and said that Karmanos could host one of those second-phase trials.

“We are currently conducting animal experiments with the single agents and the drug combination,” Dr. Burger said. “Triple-negative breast cancers might respond against that drug (AFP464).”

Triple-negative breast cancer afflicts mostly young women under the age of 40 and is more prevalent in the African-American community. About 182,460 women in the United States were diagnosed with invasive breast cancer in 2008 and about 40,480 will die from the disease, according to the American Cancer Society. Dr. Burger said that about 14 percent to 18 percent of breast cancer cases are triple-negative.

She expects that this research could translate to real-world applications in the next five years.

“These are targeted agents that are being tested,” Dr. Burger said. “Having a drug available to treat triple-negative breast cancer would be a major step in fighting this disease.”