Drug Repurposing for Advanced PC 1. Metformin Jul 29, 2014 20:35:34 GMT -8
Post by Allen on Jul 29, 2014 20:35:34 GMT -8
The anti-diabetic drug metformin may have an anti-PC effect. It is believed to act on AMPK, a substance that decreases insulin levels that might encourage cancer feeding and castrate resistance. It may inhibit the mTOR cancer growth pathway as well (see thread below). It may work
synergistically with bicalutamide and with statins. It may preferentially kill cancer stem cells and radiosensitizes cancer cells. There is a randomized clinical trial comparing metformin+Lupron to Lupron alone (NCT01620593).
Results of studies so far have been equivocal.
• A study of health records at the Mayo Clinic was published this week. It found that PC mortality was reduced by 61% among diabetics who took metformin vs insulin, by 45% vs those taking other diabetic meds, and by 31% compared to non-diabetics.
Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality
• In 2901 consecutive patients at MSK, metformin reduced the 10-yr PC mortality by 88% compared to diabetics taking other drugs, and by 67% vs non-diabetics, with significant decreases in other signs of PC progression. There was a 15-fold decrease in castrate resistance among metformin users vs diabetics who took other drugs.
Metformin and prostate cancer: reduced development of castration-resistant disease and prostate cancer mortality.
• Among 3,857 older, diabetic men, metformin use was associated with a 34% reduction in PC mortality for every 6 months of use.
Metformin Use and All-Cause and Prostate Cancer–Specific Mortality Among Men With Diabetes
Several studies have failed to show any survival benefit for prostate cancer:
The use of metformin in patients with prostate cancer and the risk of death.
Association of diabetes mellitus and metformin use with biochemical recurrence in patients treated with radical prostatectomy for prostate cancer
Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival.
Association Between Metformin Use and Risk of Prostate Cancer and Its Grade
Metformin does not affect risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database.
Effect of metformin on prostate cancer outcomes after radical prostatectomy.
Metformin Does Not Affect Cancer Risk
Whatever its efficacy may turn out to be, at least metformin is a relatively safe drug for both diabetics and non-diabetics when taken moderately.