Avastin and Sutent, two cancer drugs, do not lead to longer survival in breast cancer patients, probably because they encourage an increase in the number cancer stem cells in breast tumors, according to a study carried out on mice by researchers from the Michigan Comprehensive Cancer Center, and published in the Proceedings of the National Academy of Sciences (early edition).
Even though Sutent (sunitinib) and Avastin (bevacizumab) do shrink breast cancer tumors and slow down the rate at which the cancer develops, their effects are short-lived - the cancers starts growing again and metastasizes (spreads).
Study author Max S. Wicha, M.D., wrote:
"This study provides an explanation for the clinical trial results demonstrating that in women with breast cancer antiangiogenic agents such as Avastin delay the time to tumor recurrence but do not affect patient survival.
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."
Dr. Wicha and team treated laboratory mice with breast cancer with bevacizumab and sunitinib. Both these medications stop angiogenesis - the growth and formation of blood vessels that feed a tumor. They found that these medications, when used to treat breast cancer tumors, trigger the development of more cancer stem cells. Stem cancer stem cells help a tumor grow and spread; standard treatment is generally ineffective against them. Standard treatment here means using anti- angiogenesis drugs alone.
After treating the mice with either drug, the authors reported that the total number of cancer stem cell cells grew. They believe this is because of a cellular response to hypoxia (low oxygen). They were also able to identify the pathway involved in hypoxia that activated the stem cells.
Avastin, which is FDA approved for several cancers, had its breast cancer therapy approval revoked by the Agency. The FDA said that clinical trials had demonstrated that Avastin's effects were too brief - patients would rapidly relapse, with their cancer spreading more virulently. The Agency added that Avastin had no impact on patients' survival.
The authors say that perhaps anti-angiogenesis drugs, such as Avastin and Sutent should be administered together with a cancer stem cell inhibitor to improve their efficacy. They added that according to preliminary data from an ongoing study, this approach appears to be effective.
The American Cancer Society says that by the end of 2012, over 209,000 Americans will have been diagnosed with breast cancer, and over 40,000 will have died from the disease.
Written by Christian Nordqvist