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Study questions anti-cancer mechanisms of drug tested in clinical trials
Date:1/13/2014

CINCINNATI The diabetes drug metformin is also being tested in numerous clinical trials for treating different cancers, and several studies point to its apparent activation of a molecular regulator of cell metabolism called AMPK to suppress tumor growth.

But new research appearing the week of Jan. 13 in Proceedings of the National Academy of Sciences (PNAS) suggests that activation of AMPK may actually fuel cancer growth. Researchers from Cincinnati Children's Hospital Medical Center who led the study also recommend that clinicians testing metformin for cancer treatment consider a careful re-evaluation of their clinical data.

The researchers report on extensive laboratory tests that conclude metformin does stop cancer, although not by activating AMPK. Instead, in tests involving glioma brain cancer cells, the authors found that metformin inhibits a different molecule called mammalian target of rapamycin (mTOR) that has been linked to many other cancers.

In the body, metformin also suppresses the actions of insulin and insulin-like growth factors two molecules that support cancer growth and also likely independent of AMPK, according to Biplab Dasgupta, PhD, principal investigator and a researcher in the Division of Hematology/Oncology at Cincinnati Children's.

"Our findings do not suggest that clinical trials using metformin should be stopped. Metformin appears to be a very useful drug, but the drug's mechanism of cancer suppression is not clear," Dr. Dasgupta said. "However, our findings unveil a potential role for AMPK as a tumor growth supporter, not a suppressor, in the type of cancer that we study. This is why clinicians using metformin in clinical trials should use caution during data interpretation."

Dasgupta and his research colleagues decided to tackle the question of metformin's anti-cancer properties because some studies point to AMPK as a tumor suppressor, while others have suggested it
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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