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Taubman Scholar Dr. Max Wicha: Some cancer treatments increase cancer stem cells

Ann Arbor, Mich. -- Cancer drugs designed to curb the growth of blood vessels that feed tumors have been found to increase the number of cancer stem cells in breast tumors in mice, according to a new study authored by Taubman Institute Senior Scholar Dr. Max Wicha.

That suggests a possible new explanation for why the drugs Avastin and Sutent  don't lead to longer cancer survival rates in humans.

The researchers treated mice with breast cancer using Avastin and Sutent, both of which work by stopping the growth and formation of blood vessels, a process called angiogenesis. They found that turmors treated with these drugs developed more cancer stem cells, the cells that fuel a cancer's growth and spread, and that often are resistant to standard treatment. Both the number of cancer stem cells and the percentage of cancer stem cells that make up the tumor increased after being treated with each of these therapies.

"This study provides an explanation for the clinical trial results demonstrating that n women with breast cancer, antiangiogenic agens such as Avastin delay the time to tumor recurrance but do not affect patient survival," said Dr. Wicha, director of the University of Michigan Comprehensive Cancer Center.

In 2003, Dr. Wicha was part of the U-M research team that discovered stem cells in breast cancer — the first cancer stem cells to be found in any human solid tumor.

"Our research now suggests that in order to be effective, these agents will need to be combined with cancer stem cell inhibitors, an approach now being explored in the laboratory," he said.

The researchers found that the cancer stem cells increased because of a cellular response to low oxygen, a condition called hypoxia. And they were able to determine the specific pathways involved in hypoxia that activate the cancer stem cells.

Results of the study appear online in the Proceedings of the National Academy of Sciences Early Edition.