Breast Cancer Survival - Why Avastin And Sutent Don't Help
Editor's ChoiceAcademic Journal
Main Category: Breast Cancer
Also Included In: Cancer / Oncology; Stem Cell Research
Article Date: 26 Jan 2012 - 4:00 PST
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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
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Sarah J. Conley, Elizabeth Gheordunescu, Pramod Kakarala, Bryan Newman, Hasan Korkaya, Amber N. Heath, Shawn G. Clouthier, and Max S. Wicha
PNAS January 23, 2012, doi: 10.1073/pnas.1018866109.
MLA
23 Feb. 2012. <http://www.medicalnewstoday.com/articles/240791.php>
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http://www.medicalnewstoday.com/articles/240791.php.
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Effective Combinations of Biologics
posted by Gregory D. Pawelski on 26 Jan 2012 at 12:56 pmThere are three therapeutic approaches to target cancer stem cells: small molecule inhibitors of cell signaling pathways, monoclonal antibodies against these cancer stem cells and cancer stem cell vaccines.
Dr. Wicha states: "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."
I couldn't agree more. Biologic therapy is on the ascendancy. The possibility of eradicating cancer by selective destruction of tumor blood vessels may represent an attractive therapeutic avenue. It's going to take combination anti-vascular therapy to make a difference.
Among the most sought after attributes of drug combinations is drug synergy. Synergy, defined as supra-additivity wherein the whole is greater than the sum of the parts, reflects an elegant interaction between drugs predicted on their modes of action. While some synergistic interactions can be predicted based upon the pharmacology of the agents, others are more obscure.
The functional profiling platform extensively examines the synergy between classes of drugs based on known modes of action. The application of synergy analysis may represent one of the most important applications of the functional profiling platform, enabling the exploration of both anticipated and unanticipated favorable interactions.
These analyses are revolutionizing the way newer classes of drugs are applied and has the potential to accelerate drug development and clinical therapeutics. Good outcomes require good drugs, but better outcomes require good combinations. Intelligent combinations are a principle focus of the functional profiling platform.
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