Antiangiogenesis drugs increase breast cancer stem cells in mice

Two cancer drugs that target the growth of blood vessels supplying tumors also increase the number and proliferation of breast cancer stem cells in mice, a new study from the University of Michigan reports.

The findings provide “a potential explanation for the limited clinical effectiveness of antiangiogenic agents,” the authors write. “If our results apply to the clinic, it 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,” says senior author Max S. Wicha, MD.

Although the antiangiogenesis drugs bevacizumab (Avastin) and sunitinib (Sutent) have been found to shrink breast cancer tumors and slow progression of disease temporarily, clinical trials have shown that they have limited effect on survival. (On November 18, 2011, FDA revoked its accelerated approval to treat breast cancer with bevacizumab because it failed to confer a survival benefit.)

In the University of Michigan study, when mice with breast cancer were treated with the two drugs the tumors developed more cancer stem cells, which promote growth and spread of the cancer and often fail to respond to standard treatment. Further, by generating intratumoral hypoxia, the drugs increased proliferation in the number and percentage of stem cells in the tumors. The authors also identified pathways by which the process occurred.

The study was published online January 23 in the Proceedings of the National Academy of Sciences Early Edition. 

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