Initial results from the first clinical trial targeting breast cancer stem cells show that the number of cancer-causing stem cells dropped significantly after the treatment, a U-M oncologist told a World Stem Cell Summit audience Oct. 6 in Detroit.
Dr. Max Wicha, director of the Comprehensive Cancer Center, presented some preliminary results from the recently completed Phase I/II trial, which started in 2006. The trial enrolled 35 women with metastatic breast cancer from three centers: U-M, Baylor College of Medicine in Houston and the Dana Farber Cancer Institute in Boston.
The trial involved a drug that was shown in the lab to target cancer stem cells. Called MK-0752, it is manufactured by Merck and was originally developed for treatment of Alzheimer’s disease. In the trial, MK-0752 was combined with the common chemotherapy drug docetaxel. Cancer stem cells have been shown to be resistant to many forms of chemotherapy, though the drugs are effective against other tumor cells.
The ultimate goal of this approach would be to reduce the number of stem cells as well as the nonstem cells that make up the bulk of the tumor. Researchers believe targeting both cell populations is key to killing the cancer.
“In nine of the 35 patients, we did biopsies before and after the treatments,” Wicha said. “We measured the stem cells, and we did demonstrate that we knocked down the stem cells significantly with this treatment.
“Some of the patients appear to have done very well, but you can’t say for sure it’s because of the stem cell drug — because after all, they did get chemotherapy, too,” he said. “But these early results are encouraging.”
The principal investigator of the Phase I/II study was Anne Schott, an associate professor of internal medicine at the Medical School. It’s now up to Merck to decide how to proceed with follow-up studies, Wicha said on the final day of the summit. U-M was one of the event’s sponsors.
The cancer stem cell model states that a handful of rogue stem cells drive the formation and growth of malignant tumors in many cancers. Proponents of the idea have been pursuing innovative treatments that target these rare stem cells.
Cancer stem cells are believed to represent 1 to 3 percent of all the cells in a tumor but are the only cells capable of regenerating new cancer cells, according to the model, which is not universally accepted. “If the cancer stem cell is left intact, it’s like a root of a plant, and it just regenerates tumors,” Wicha said.
U-M researchers, including Wicha, were the first to identify cancer stem cells in solid tumors, finding them in breast cancer tissue in 2003. Cancer stem cell research has exploded worldwide, especially over the past five years. The Comprehensive Cancer Center has several cancer stem cell-related clinical trials either underway or about to begin, said Wicha, a medical oncologist who specializes in breast cancer.
“It’s a very exciting area and has been a major focus of the research at our cancer center,” he said. “We’ve probably done more cancer stem cell studies than any other center in the world.”
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