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Rich66 · 10-02-2009, 11:58 PM

http://www.diabeteshealth.com/read/2...r-wonder-drug/

Mighty Metformin: The New Cancer Wonder Drug

Sep 25, 2009

Metformin has always been the old reliable for treating new onset type 2 diabetes, but it's beginning to look like it's got a new calling as a cancer treatment. Diabetes Health recently reported on the fact that metformin reduces a type 2 person's risk of pancreatic cancer by up to 62 percent. It's also been observed that people with type 2 who take metformin have a much lower cancer incidence than those who don't. Now it appears that metformin can help with breast cancer treatment as well. A study of mice with breast cancer generated from human breast cancer cells has found that they remained tumor-free for nearly three months on metformin combined with doxorubicin, a standard cancer chemotherapy. In mice given only the doxorubicin, the tumors recurred.
How metformin suppresses cancer has been unclear, but now researchers believe that they may have the answer. According to Dr. Kevin Struhl of Harvard Medical School, the lead researcher of the study, metformin selectively kills cancer stemcells. This is an extremely valuable talent because stem cells, which make up five to ten percent of a tumor's cells, are resistant to chemotherapy. Although standard chemotherapy kills the mature cancer cells that comprise most of the tumor, it can't vanquish the cancer stem cells. Consequently, the tumor is able to regrow after standard chemotherapy. But the combination of standard chemo and metformin appears to be very powerful.
The researchers hope that by adding metformin to the cancer treatment regimen, it will be possible to reduce the dose of standard chemo. According to Dr. Struhl, current chemo regimens load patients up with as much as they can possibly tolerate. With metformin, however, the doses of standard chemo could possibly be reduced, allowing good results with fewer side effects.
Dr. Struhl's study grew out of another project, during which he found that the gene activity changes that occur when cells transform into cancer are a lot like what goes on in diabetes and other inflammatory conditions. He reasoned that if a common genetic pathway underlies different diseases, drugs that work against one disease might also work against another. After screening a number of drugs, he found that metformin was most effective in inhibiting cells from transforming into cancer. Those findings led to his current study, the results of which were published in the September 14 online edition of Cancer Research, a journal of the American Association for Cancer Research.
Although the current research was conducted on mice, their cancer cells were actually of human origin, which is promising. The researchers are now planning clinical trials conducted on humans. This normally lengthy process might be hastened by the fact that metformin is already an accepted drug that is known to be safe. In fact, a clinical trial to see if metformin alone is effective in preventing breast cancer from recurring in early stage breast cancer patients who have already had surgery and chemo will begin enrolling patients next year.
Interestingly, Dr. Struhl and Harvard Medical School have already applied for a patent that would cover a combination of metformin and a lower dose of chemotherapy to treat cancer.

Breast Cancer Res Treat. 2009 Nov 22. [Epub ahead of print]
Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy.

Phoenix KN, Vumbaca F, Fox MM, Evans R, Claffey KP.
Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT, 06030-3501, USA.
Dietary energy restriction has been shown to repress both mammary tumorigenesis and aggressive mammary tumor growth in animal studies. Metformin, a caloric restriction mimetic, has a long history of safe use as an insulin sensitizer in diabetics and has been shown to reduce cancer incidence and cancer-related mortality in humans. To determine the potential impact of dietary energy availability and metformin therapy on aggressive breast tumor growth and metastasis, an orthotopic syngeneic model using triple negative 66cl4 tumor cells in Balb/c mice was employed. The effect of dietary restriction, a standard maintenance diet or a diet with high levels of free sugar, were tested for their effects on tumor growth and secondary metastases to the lung. Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals. Long-term metformin treatment demonstrated moderate yet significant effects on primary tumor growth, most significantly in conjunction with the high energy diet. When compared to the control diet, the high energy diet promoted tumor growth, expression of the inflammatory adipokines leptin and resistin, induced lung priming by bone marrow-derived myeloid cells and promoted metastatic potential. Metformin had no effect on adipokine expression or the development of lung metastases with the standard or the high energy diet. These data indicate that metformin may have tumor suppressing activity where a metabolic phenotype of high fuel intake, metabolic syndrome, and diabetes exist, but may have little or no effect on events controlling the metastatic niche driven by proinflammatory events.

PMID: 20204498 [PubMed - as supplied by publisher]

10-02-2009, 11:58 PM	#13
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Common Diabetes Drug May 'Revolutionize' Cancer Therapies: Unexpected T-cell Brea http://www.diabeteshealth.com/read/2...r-wonder-drug/ Mighty Metformin: The New Cancer Wonder Drug Sep 25, 2009 Metformin has always been the old reliable for treating new onset type 2 diabetes, but it's beginning to look like it's got a new calling as a cancer treatment. Diabetes Health recently reported on the fact that metformin reduces a type 2 person's risk of pancreatic cancer by up to 62 percent. It's also been observed that people with type 2 who take metformin have a much lower cancer incidence than those who don't. Now it appears that metformin can help with breast cancer treatment as well. A study of mice with breast cancer generated from human breast cancer cells has found that they remained tumor-free for nearly three months on metformin combined with doxorubicin, a standard cancer chemotherapy. In mice given only the doxorubicin, the tumors recurred. How metformin suppresses cancer has been unclear, but now researchers believe that they may have the answer. According to Dr. Kevin Struhl of Harvard Medical School, the lead researcher of the study, metformin selectively kills cancer *stemcells. This is an extremely valuable talent because stem cells, which make up five to ten percent of a tumor's cells, are resistant to chemotherapy. Although standard chemotherapy kills the mature cancer cells that comprise most of the tumor, it can't vanquish the cancer stem cells. Consequently, the tumor is able to regrow after standard chemotherapy. But the combination of standard chemo and metformin appears to be very powerful. The researchers hope that by adding metformin to the cancer treatment regimen, it will be possible to reduce the dose of standard chemo.* According to Dr. Struhl, current chemo regimens load patients up with as much as they can possibly tolerate. With metformin, however, the doses of standard chemo could possibly be reduced, allowing good results with fewer side effects. Dr. Struhl's study grew out of another project, during which he found that the gene activity changes that occur when cells transform into cancer are a lot like what goes on in diabetes and other inflammatory conditions. He reasoned that if a common genetic pathway underlies different diseases, drugs that work against one disease might also work against another. After screening a number of drugs, he found that metformin was most effective in inhibiting cells from transforming into cancer. Those findings led to his current study, the results of which were published in the September 14 online edition of Cancer Research, a journal of the American Association for Cancer Research. Although the current research was conducted on mice, their cancer cells were actually of human origin, which is promising. The researchers are now planning clinical trials conducted on humans. This normally lengthy process might be hastened by the fact that metformin is already an accepted drug that is known to be safe. In fact, a clinical trial to see if metformin alone is effective in preventing breast cancer from recurring in early stage breast cancer patients who have already had surgery and chemo will begin enrolling patients next year. Interestingly, Dr. Struhl and Harvard Medical School have already applied for a patent that would cover a combination of metformin and a lower dose of chemotherapy to treat cancer. Breast Cancer Res Treat. 2009 Nov 22. [Epub ahead of print] Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy. Phoenix KN, Vumbaca F, Fox MM, Evans R, Claffey KP. Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT, 06030-3501, USA. Dietary energy restriction has been shown to repress both mammary tumorigenesis and aggressive mammary tumor growth in animal studies. Metformin, a caloric restriction mimetic, has a long history of safe use as an insulin sensitizer in diabetics and has been shown to reduce cancer incidence and cancer-related mortality in humans. To determine the potential impact of dietary energy availability and metformin therapy on aggressive breast tumor growth and metastasis, an orthotopic syngeneic model using triple negative 66cl4 tumor cells in Balb/c mice was employed. The effect of dietary restriction, a standard maintenance diet or a diet with high levels of free sugar, were tested for their effects on tumor growth and secondary metastases to the lung. Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals. Long-term metformin treatment demonstrated moderate yet significant effects on primary tumor growth, most significantly in conjunction with the high energy diet. When compared to the control diet, the high energy diet promoted tumor growth, expression of the inflammatory adipokines leptin and resistin, induced lung priming by bone marrow-derived myeloid cells and promoted metastatic potential. Metformin had no effect on adipokine expression or the development of lung metastases with the standard or the high energy diet. These data indicate that metformin may have tumor suppressing activity where a metabolic phenotype of high fuel intake, metabolic syndrome, and diabetes exist, but may have little or no effect on events controlling the metastatic niche driven by proinflammatory events. PMID: 20204498 [PubMed - as supplied by publisher]