“There is now actually a fairly large body of evidence to support a role for metformin as cancer therapy,” Dr Decker told Cancer Therapy Advisor. “There are a number of retrospective studies that suggest that patients with lung, breast, pancreatic, or even gynecologic cancer who are taking metformin have better survival.”

“But importantly, there are also several similar studies that failed to show any benefit,” Dr Decker was quick to add. “For this reason, it’s critical that these findings be confirmed with clinical trials, and several such studies are underway. For lung cancer, there’s an ongoing trial sponsored by the NRG that’s examining the addition of metformin to standard therapy in patients with locally advanced lung cancer, the same population that was examined by Wink et al.”


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Researchers at the Rutgers New Jersey Medical School in Newark found no hint of metformin predicting NSCLC survival in either univariate or multivariate analyses, noted lead study author Narjust Duma, MD. Her team’s study did find that statins (but not metformin) were associated with NSCLC survival.2

“We just don’t know yet, to be honest,” she cautioned. “In our study, metformin didn’t make a difference. […] We don’t have a randomized controlled study with metformin only, to say yes, it is working.”

“I won’t recommend metformin to be used as a drug for lung cancer patients because there is not yet enough evidence to use it only for that,” Dr Duma said. “But we can say that if they are already on metformin [for diabetes], we may see some benefit.”

It’s a crucially important question, she emphasized.

“Our population is getting older every day and they are on many other medications; studying these drugs is a priority. I think their use of all of these medications is the next phase of research for the next 10 years,” she said.

There are biologically plausible mechanisms whereby metformin could slow tumor progression, but these remain largely hypothetical, experts agreed.

Repurposing metformin as a cancer therapy has major challenges ahead.3

“To make metformin an effective anti-cancer therapy in clinical [practice], we need to solve 2 problems,” said Lei Xie, PhD, an associate professor in Computer Science at Hunter College, CUNY in New York, NY. “First, what is the molecular mechanism of metformin’s anti-cancer effects? Second, what is the biomarker that can distinguish anti-cancer response of metformin in different individuals?”

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“Metformin reduces the levels and cellular uptake of insulin, which implies a decrease in activation of insulin receptors,” agreed Dr Decker. “This results in decreased activation of several signaling pathways including RAS/Raf/Mek/Erk, and PI3K/AKT/mTOR, which are known to be highly activated in some cancers. But it is important to note that there’s no convincing existing evidence that this is actually happening.”

References

  1. Wink KCJ, Belderbos JSA, Dieleman EMT, et al. Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy. Radiother Oncol. 2016;118(3):453-459.
  2. Durma N, Kang M, Abu-Ihweij K, et al. Effect of statins and metformin on survival in patients with non-small cell lung cancer (NSCLC). Chest. 2015;148(4_MeetingAbstracts):594A.