Max S. Wicha, M.D., is director of the U-M Comprehensive Cancer Center.

Perilous Approach

Anti-angiogenic drugs promote growth of breast cancer stem cells

issue 15 | Spring 2012

Cancer treatments designed to block the growth of blood vessels were found to increase the number of cancer stem cells in breast tumors in mice, suggesting a possible explanation for why these drugs don't lead to longer survival, according to a study by researchers at the U-M Comprehensive Cancer Center.

While anti-angiogenic drugs do shrink tumors and slow the time until the cancer progresses, the effect does not last, and the cancer eventually regrows and spreads.

Breast cancer stem cells in a region of hypoxia in a mouse treated with the anti-angiogenic drug sunitinib (Sutent).

"This study provides an explanation for the clinical trial results demonstrating that in women with breast cancer, anti-angiogenic agents such as Avastin delay the time to tumor recurrence but do not affect patient survival," says study author Max S. Wicha, M.D., director of the U-M Comprehensive Cancer Center.

The researchers treated mice with breast cancer using the anti-angiogenesis drugs Avastin (bevacizumab) and Sutent (sunitinib). The researchers found that tumors treated with these drugs developed more cancer stem cells, which fuel a cancer's growth and spread and are often resistant to standard treatment.

The researchers found the increase in cancer stem cells was due to hypoxia. They were also able to determine the specific pathways involved in hypoxia that activate the cancer stem cells.

The U.S. Food and Drug Administration recently revoked approval of Avastin for treating breast cancer. The reversal was in response to clinical trials showing that the drug's benefit was short-lived, with breast cancer patients quickly relapsing and the cancer becoming more invasive and metastatic.

The current study, published in the Proceedings of the National Academy of Sciences, suggests the possibility of combining anti-angiogenesis drugs with a cancer stem cell inhibitor to enhance the benefit of this treatment. The researchers are testing this approach in mice, and preliminary data looks promising.

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