Two breast cancer drugs, Avastin and Sutent, may inadvertently aid cancer growth, a study in mice suggests. The drugs, designed to reduce the blood supply to tumours, were found to encourage cancer stem cell growth, potentially fuelling the spread of the cancer. The study, published in PNAS, may explain why patients treated with Avastin are at risk of relapsing and why these drugs fail to improve overall survival rate despite initially slowing the tumour's growth.
In the study, scientists at the University of Michigan treated mice that had breast cancer with Avastin and Sutent (chemical names bevacizumab and sunitinib). The drugs stop new blood vessels forming, a process called angiogenesis, so that the supply of food and oxygen to the tumour is reduced.
The cancer stem cells in the tumours of the treated mice were mostly found in pockets of low oxygen concentration, created, paradoxically, by the reduction in oxygen delivery. Cancer stem cells fuel the spread and growth of a tumour and are difficult to eliminate with radiotherapy and chemotherapy.
However, Dr Max Wicha, who led the study, suggests that such anti-angiogenic drugs may still be important in cancer therapy if used in conjunction with other drugs. 'These agents will need to be combined with cancer stem cell inhibitors, an approach now being explored in the laboratory', he said.
Avastin is currently licensed to treat breast cancer in the UK yet not available on the NHS. The UK's National Institute for Health and Clinical Excellence advised against its use in February 2011, finding insufficient evidence that it prolongs life. The drug was approved by the US Food and Drug Administration for breast cancer in 2008, but this decision was revoked in November 2011. Sutent is not prescribed for breast cancer in the UK or the USA.
Despite the negative findings on Avastin, two studies this week have suggested that it may be useful in treatment during the early stages of breast cancer. Separate studies, performed on 1,200 and 1,900 women, and both published in the New England Journal of Medicine, looked at the use of the drug prior to surgery. They both found that Avastin significantly reduced or even eliminated the tumour, making it easier to operate on. These were initial findings - the longer-term survival rate of women given Avastin pre-operatively is as yet unknown.
Sources and References
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Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia
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Avastin, Sutent increase breast cancer stem cells, U-M study shows
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Breast Cancer Survival - Why Avastin And Sutent Don't Help
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Lab Paradox May Explain Avastin's Effects
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Avastin fights early breast cancer in 2 studies: Will it be re-approved?
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Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer
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Neoadjuvant Chemotherapy and Bevacizumab for HER2-Negative Breast Cancer
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