Metformin may help slow progression, reduce risk of certain cancers

NEW YORK — A medication commonly prescribed for patients with Type 2 diabetes also may play a critical role in patients at risk of developing certain cancers.

In three separate studies published in Cancer Prevention Research, a journal of the American Association for Cancer Research, findings showed how metformin may protect against oral cancer and liver cancer, as well as slow the growth rate of prostate cancer among men prior to prostatectomy.

In the oral cancer study, J. Silvio Gutkind, chief of the Oral and Pharyngeal Cancer Branch of the National Institute of Dental and Craniofacial Research at the National Institutes of Health, and colleagues found that administration of metformin reduced the size and number of carcinogen-induced oral tumoral lesions in mice and significantly reduced the development of squamous cell carcinomas by about 70% to 90%. "We saw strong activity against mTORC1 (mammalian target of rapamycin complex 1), which we know contributes to oral cancers, so this is strong preclinical information that there is a protective effect," Gutkind said.

In a study led by Geoffrey Girnun, an assistant professor in the department of biochemistry and molecular biology at the University of Maryland School of Medicine, found that after he and his colleagues chemically induced liver tumors in mice, the mice taking metformin displayed minimal tumor activity, while the control mice displayed significant tumor growth. Girnun's team also showed that metformin prevented liver cancer in part by inhibiting lipid synthesis in the liver, a process known to promote cancer. Girnun currently is planning a clinical trial in patients at risk for liver cancer to determine if the chemopreventive qualities observed in mice are confirmed in humans.

"Since many of the effects of the drug take place in the liver, we were surprised when we reviewed the literature that there was no direct evidence for a protective effect of metformin in liver cancer except for a few retrospective epidemiological studies," Girnun said.

Meanwhile, in a mid-stage clinical trial conducted by Anthony Joshua, staff medical oncologist at the Princess Margaret Hospital of the University Health Network in Toronto, and colleagues evaluated 22 men with confirmed prostate cancer who had been assigned up to 500 mg of metformin three times a day prior to undergoing prostatectomy. Patients were assigned metformin for a median duration of 41 days. During that time, none of the men reported "grade-3 adverse events" and all of them underwent prostatectomy with no adverse effect related to use of metformin.

"Although these are preliminary results, metformin appeared to reduce the growth rate of prostate cancer in a proportion of men," Joshua said. "Also, it appeared to reduce one of the main growth pathways that may have contributed to the overall growth of the tumor ... "This research builds on the hypothesis that metformin has a role in prostate cancer. Exactly what that role will be will depend on the results of the analysis currently being completed by our study team and others worldwide."

For more information on these studies, visit AACR.org.


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