May 29, 2023

Prof Pollack speaks with ecancertv at the 2016 BACR and ECMC Joint Meeting about the repurposing of metformin to treat cancer.

Well i gave a review of the current status of research on the anti-diabetic drug metformin in terms of repurposing it for applications in oncology and we drew a distinction between using the drug for prevention and using the drug for treatment of existing cancers and the take-home message is that really we have lots of rationale for suspecting that metformin might

Have utility but we have very little data to actually demonstrate that so it’s best regarded as research in progress and even though many people have strong opinions on this subject some people believing that metformin should be almost put in the drinking water because it’s so obviously useful and other people having the opposite view saying that this is just kind

Of an epiphenomenon that it has something in mice but is really clinically irrelevant neither of those extremes in my view accurately reflects the current state of research where we in fact have some an unanswered questions and answers to these questions will you know are expected within the next few years question of why metformin ever became to be studied in the

By oncologists probably relates mainly to pharmacal epidemiology studies that were carried out about a decade ago where diabete ologists were just interested in reviewing their records and seeing how their patients were dying and some died of heart attacks and some died of strokes and some died of cancer and in reviewing their records they found in some cases and

Some highly cited studies that fewer diabetic patients were dying of cancer than expected if their diabetes was treated with metformin so that’s what got the issue on the scientific agenda it got even higher on the scientific agenda when laboratory studies with metformin appeared to show that metformin was slowing the growth of cancer cells and laboratories and it

Appeared at one point maybe eight to ten years ago that we had strong evidence both from the laboratory and from retrospective pharmaco epidemiology that metformin really has showed a lot of promise but since that time as is often the case with research we’ve recognized it’s much more complicated and in the case of the retrospective pharmaco epidemiology studies

Those were initially taken as as very strong evidence but there’s been now with more time going by other studies that failed to replicate those initial exciting results showing that diabetics treated with metformin had less cancer and there been statistical arguments indicating that maybe some of the exciting studies or statistically flawed so that the population

Evidence from these retrospective studies is now regarded by most experts as highly controversial rather than proving a point i don’t mean to imply that we are certain that the opinion of that the controversies resolved and that the pharmacal epi studies prove no association rather we now have gone from an earlier stage where the association was thought to be

Very real and very interesting to the current state of affairs where the population evidence is now regarded as controversial and a recognition that we need prospective clinical trials to really sort it out in terms of efficacy and in terms of little buret ori studies these laboratory studies in contrast are very reproducible some of the effect sizes are large and

Easy to replicate and they have been replicated around the world but there there’s been different discussions having to do with the exposure levels and dosing levels are those interesting doses that always seem to work in mice in certain mice models are those doses really the doses that are relevant for humans and that’s also being a point of some discussion so

That really if we put it all together metformin is a very interesting agent it certainly works for diabetes and i would have to summarize now that it remains very active in terms of a cancer research topic but we don’t have definite answers and it really fits into a more general interest or research theme in oncology which is oncology metabolism and this is you

Know metformin research represents a small part of overall cancer metabolism research because we do recognize that metformin works fundamentally by inhibiting oxygen phosphorylation or the burning of carbohydrate fuels to create energy and that mechanism is is is very appealing because we know that cancers have a high need for you know they’re they’re vulnerable

To strategies that deprive them of the energy that they need the whole agenda for metformin itself is can this anti diabetic be repurposed for either cancer treatment or cancer prevention and i feel that that question is unanswered but this intensive research there’s another area of research that deserves mention which is the synthesis of analogs of metformin that

Are specifically designed to be antineoplastic agents because there they they affect energy metabolism in a way that’s more potent than the effects of metformin and several pharmaceutical companies are now exploring that area synthesizing new drug candidates based on the structure of metformin that is new by kwan ides and these may be taken towards clinical trials

Some of those might be a little bit more toxic than that form in itself but maybe much more efficacious and that agenda is i would emphasize for cancer treatment not for cancer prevention for cancer prevention you need an agent that has absolutely demonstrated safety because you’re giving a drug to healthy people so for cancer prevention the agenda is metformin

Itself for cancer treatment we may be able to have more potent versions of metformin and hope that their toxicity is such that they’ll find that sweet spot where the toxicity will be acceptable but the efficacy may be better than that foreman prevention is a very difficult it’s a harder job to do research in the prevention field than it is in the treatment field

Chiefly because obviously if you have a cancer patient and you have a new agent it’s quite easy to determine whether it works you just have to wait a few weeks or months of treatment and either you’re pleased or you’re displeased if your goal is to prevent you actually have to study populations over many years or decades to determine whether a given intervention

Has worked so at the meeting here we have not really heard about any breakthroughs and i think that that is the reason that it just one needs to have a lot of patience to work in the field of cancer prevention despite the challenges of the methodological challenges of working in prevention where timelines have to be so long before you can draw conclusions i feel

That prevention research is absolutely essential because of the state of the art of treatment research cancer treatment even with our best newest treatments tends to be less effective than we would like and more expensive than we’d want so that notwithstanding the challenges cancer prevention research has to be part of the overall cancer control strategy because

If even at a pessimistic view a quarter of cancers could be prevented and some people would argue it’s closer to 50% but even if it’s only a quarter of cancers that could be prevented we have to do that so that so that our treatment facilities you know have less to work on and or fewer patients to see because if especially if you take a global perspective the rates

Of increase of cancer and a global basis are frightening and we still really don’t have cheap and effective treatment mechanisms that would be usable in many of the countries that are facing upcoming optics and cancer incidents so despite the challenges of cancer prevention we feel we have to strongly push the envelope there and and do as much as we can

Transcribed from video
Metformin in cancer prevention By ecancer