Common Diabetic Drug Fights Cancer Stem Cells

SubtleGuest writes "In the latest issue of Cancer Research, a breakthrough study shows that Metformin, a cheap and common diabetic medicine, kills cancer stem cells — the cells postulated to be responsible for tumor resistance and recurrence after chemotherapy (research abstract here). It has been known that diabetics taking Metformin experience lower cancer rates, and now it is apparent why that may be and how it may apply to non-diabetics as well. When combined with Doxorubicin to kill non-stem cancer cells, the results are nothing short of astonishing: total remission in a mouse xenograft model. The results are achieved at levels below the dosage needed for diabetic control, opening many new avenues in cancer treatment and prevention."

Comments

I feel jealous

[BadAnalogyGuy]

I wish I was a mouse. Then I'd get all the good cancer treatments.

Re:I feel jealous

[geegel]

Well... you'd get the bad ones too.

Re:I feel jealous

[Metasquares]

Many of the mice used in research are transgenic; that is, they're genetically modified in such a way that they're predestined to develop cancer. Others, such as the mouse described in the summary, have tumors implanted in them. When testing a treatment (rather than a cause), exposure to environmental carcinogens to promote development of a tumor is less common.

In any case, be glad you're not a lab mouse. Sometimes even the survivors are killed off at the end of the experiment (though this is becoming less common, particularly in cases where the mice are left in no lasting pain or disability).

Re:I feel jealous

[siloko]

I really, really, really want to post a Whooosh but your reply was so nice and informative I couldn't bring myself to do it!

Cruel and unusual punishment

[cjfs]

How metformin affects cancer isn't certain, but one possibility is that it deprives tumor cells of sugar.

It's a slippery slope. If we allow this treatment to go through, what next? Take away their caffeine?

What use is there in victory if we destroy all we stand for?

Re:Cruel and unusual punishment

[Nick Number]

It's a slippery slope. If we allow this treatment to go through, what next? Take away their caffeine?

After that we cut off their supply of Robert Smith tunes.

That's right; no Cure for cancer say I.

Non-human model systems

[sumthinboutjesus]

I think we shouldn't get overexcited yet; these results have only been shown in a mouse xenograft model i.e. a mouse that has human tissue transplanted. Normally these mouse models are completely immunodeficient or else they wouldn't be able to accept a human transplant. Translating these results into some meaningful treatment for normal adults is highly likely to face a lot of roadblocks and complexities. The human immune system alone is much more complex than the mouse immune system, so you have to remember that animal models more often than not don't translate into meaningful human results. Sometimes they do, and that why model organisms exist, but I'm not putting my eggs in this basket just yet; when I see double blind randomized controlled human trials show positive results then I might believe this has potential to work.

Re:Non-human model systems

[radtea]

Translating these results into some meaningful treatment for normal adults is highly likely to face a lot of roadblocks and complexities.

I generally agree with this, but there are two things that raise this above the usual "cures cancer in mice" hype.

The first is that these are xenografts, which means they're dealing with authentic human cancers, which are in general far tougher to kill than cancers in other species (we are tuned up for great longevity for obvious evolutionary reasons, and therefore incredibly cancer resistant compared to most species, meaning the few human cancers that do become malignant are incredibly hard to kill.) A quick look at the paper shows they've used multiple cell lines for the xenographs, which is also good.

The second is that there is already evidence of reduced cancer rates in humans taking this stuff (pancreatic cancer only, and diabetics only, so limited but suggestive data.)

The full paper is available at:

http://cancerres.aacrjournals.org/cgi/reprint/69/19/7507

and it really is one of the few on the topic that I'd honestly say has results that can fairly be characterized as "dramatic".

You're right: they may lead to another dead end. We've seen a lot of those before. But this looks like solid research and very promising results. Clinical trials on humans are in the works, with patient enrollment starting perhaps as soon as next year.

Re:Non-human model systems

[jimicus]

Hang on a minute, you sound like you know what you're talking about! What are you doing on /.?

Re:Non-human model systems

[Svartalf]

The interesting thing is that it's Metformin... That drug does several things at once (though it's side-effects make it such that you largely don't want it for it's carb-blocking ability...)- diabetics on that med tend to lose weight if they're solely on that one and abide by diet restrictions and are compliant with it. It'd be interesting what comes of the research.

Re:Non-human model systems

[moon3]

This drug regimen is $4/months cheap -- this might threaten the whole cancer industry. I bet results of this trial will disappear quickly or some 'sponsored' research will soon came with a counter claim.

Re:Non-human model systems

[RightSaidFred99]

Yeah, just like those magic cars everyone just knows "they" have but that the big mean oil companies managed to stop. And all those wonderful herbal remedies to cancer that those "fat cats" don't want us to use and that cure cancer in a mere few weeks.

Paranoia for the win!

Re:Non-human model systems

[EndlessNameless]

"I deleted a file two years ago and defragmented my hard drive. You should be able to get it back for me, right?"
 
Don't comment on how simple something should be if you have no understanding of the problem.

  But isn't prudent to get the cancer cells into some ecosystem or bioreactor, apply various factors and study them there instead of this Nazi like trial and error research involving those animals ?
 
If this were feasible, we would have started experimenting on human cancers directly as soon as the first petri dishes rolled out.

  They claim to be able to sequence much smaller DNA so why not 'sequence' or look into the cancer here.
 
Sequencing DNA is many, many steps away from having adequate detail regarding the biochemical differences that will manifest in the organism (or cell). We can't even coimpletely simulate a bog-standard conception-to-birth timeline for typical humans, with various genes switching on and off at different locations and times during development. There are tremendous advances taking place in genetics and will be for some time---but we are nowhere near this level of sophistication at present.

  Also inside organisms they are able to highlight and target cancer with some agent and see exactly where the cancer cells are using that PET scanner technique, but unable to use the same path to deliver treatment to those areas.
 
The 'P' in PET scanner stands for positron. If the treatment could home in on positron concetrations then you're golden. I'll tell you what: you get the positron-homing molecules ready and I'll find a way to superglue the medicinal molecules to them. Deal?

  It seams to me that this cancer 'industry' is trying to do prolonged and expensive healing, but not to cure.
 
It only seems that way because you are utterly ignorant of the underlying reality.

I'm diabetic...

[bughunter]

... and Metformin was one of the first drugs I tried. Too bad it made me feel HORRIBLE .

Not just all caps horrible, but bold and italic horrible, too. Fever, nausea, chills, cramps, and headache. We even tried ramping up the dose, starting in very small amounts, to no avail. Only afterward did the doctor tell me that a significant fraction of the population has the same reaction.

(I finally broke down and just took insulin and Actos. Works great to control blood sugar. Also works great for gaining weight.)

Re:I'm diabetic...

[JerryLove]

I had cancer and they gave me chemo (then a high-doseage chemo (bone-marrow transplant)). That wasn't a pleasent feelign either.

Still, I doubt Metformin would have had the permenant effects that did.

Re:I'm diabetic...

[Frankie70]

Did you try the extended release Metformin - for many people that has lesser
side effects than the regular one.
The most common side effect of Metformin is an upset stomach & lots of farting.
But usually that subside after a month or so.

Metformin is really a wonder drug - if possible every diabetic should take it
- It's the one of the few diabetic medication which doesn't make you put on weight.
It usually results in a 3-4 pound weight loss.

- It never causes low blood sugar.

- It's cardioprotective. Diabetics on metformin reduce their chances of getting a heart
attack.

- It's dirt cheap if you take the generic.

- It helps with the Dawn Phenomenon

It help starting with a very low dose of Metformin ER - say Metformin 500 Extended Release
once a day for a couple of weeks to see how it works for you - if you haven't already
tried the ER yet - then you can keep increasing dose - 750, 1000, 1500, 2000 till you find
the maximum dose you can tolerate.
If

Re:I'm diabetic...

[bughunter]

Metformin ER was what I started with. Didn't tolerate that at all, and tried the smallest tablets of the basic formula. That sucked, too, so I tried the syrup in very small doses, and tried to endure mild symptoms for a week, before ramping up to larger doses, but I never could build a tolerance to it.

The elephant in the room...

[Fished]

It's worth mentioning that low-carb diets have also been shown (at least preliminarily) to restrict tumor growth. See http://www.time.com/time/health/article/0,8599,1662484,00.html. I wonder whether part of Metformin's effect might be related to it's lowering of blood sugar, above and beyond the direct biochemical mechanism mentioned in the article.

Is medical advancement stagnating?

[Kirin Fenrir]

I never quite understand these stories; maybe it's because I have difficulty grasping the complexities of medicine (as many people do and aren't aware they do), but doesn't it seem like the discovery of a treatment and the implimentation of a treatment have become abnormally distant from one another? Far beyond what proper testing and trials should mandate?

Is this a patent problem?
A legal one?

It's starting to seem like we've all but halted the advance of medicine while we try to extract as much profit from each new discovery as possible, nevermind that real people are dying in the meantime. How long is it before this drug treatment is avaliable? 2025?

Again, I have little grasp of medicine, so maybe I'm being paranoid. Can anyone give greater perspective on my concern?

Re:Is medical advancement stagnating?

[maxume]

The frequency with which potential treatments are announced has increased, and the number of existing, effective treatments has increased (both of these pretty much work since whenever).

So you see more noise about things that might work, and those things face a higher bar when actually tested out, thus there are more failures.

If you step back and look at survival rates for various cancers, they have gone up significantly, even in just the last 10 years (some of this may simply be due to increased awareness of carcinogens, but some of it is likely to be due to better treatments).

Re:Is medical advancement stagnating?

[yamfry]

Over the decades, yes, it has been taking longer to go from discovery to clinical implementation. Back before 1906, there were no regulations on the sale of drugs from a safety standpoint. A number of medication safety events led to the complex framework fo regulations currently in place. Concern about shady salesmen selling snake oil without safety or effectiveness, the thalidomide tragedy, the Vioxx debacle, and other events formed the public support for regulating drugs and biologicals. Right now there are 4 phases of human trials that drugs have to go through for approval (in the USA, anyway) -- on healthy volunteers, on a small sample of "sick" people, on a large sample of "sick" people, then follow-up from post-clinical studies. And that has to be preceded by specific animal studies with approval of an IND. There are a number of work-arounds for expediating cancer drugs, and the FDA is always finding ways to streamline and expediate the approval process without hindering the safety evaluation they are charged with. For further info:
On clinical trials
History of FDA oversight
On the Current act
Again, I apologize for the US-centric linkage. Also, I do not work for the FDA :)

Re:Is medical advancement stagnating?

[werfele]

How long is it before this drug treatment is avaliable? 2025?

It's available now. Doctors in the U.S. are allowed to prescribe medication for off-label uses if it's approved for any use, so you might be able to get a prescription metformin for anti-cancer use this afternoon if you make a few calls. There may be a more general problem, but this is not a good illustration of it.

Re:Is medical advancement stagnating?

[fuzzyfuzzyfungus]

It'll probably be a bit faster in this case(since the drug in question is already approved, and has a decent amount of clinical history, for diabetic use, the question of safety should already be mostly addressed); but the problem, in general, is that the point where media reports of "discovery of a treatment" start to occur tends to be somewhere in the "promising animal research" stage or even in the "intriguing in vitro results" stage.

At that point, you still have to move on and make sure that it doesn't kill humans(inordinately often, that is, risks are worth it if the disease, or the current best care has worse risks) which takes time and careful testing, and that it actually has the effect desired in humans, more time and testing, and finally roll out.

Drug companies are, undoubtedly, willing to behave downright evilly when it is in their interests. In this case, though, their interests are largely aligned in favor of the swiftest deployment possible. Every day you are working on a drug and unable to sell it, you are losing money on that drug. If your competitor has a drug and you introduce a new one that does the same thing or better, you'll gain some market share. Even if the existing drug is your drug, its patent protections are ticking away, and you really want to have something new ready to go before they expire. You could try just sitting on a new drug, and milking the old one; but, if you patent the new one, its patent protections will also be ticking away, so you'd be insane not to start selling it, and if you don't patent, somebody else might.

You'll note, as well, that most of the stories of drug company malfeasance involve playing up the drug's efficacy or playing down its risks, or pushing doctors to switch from old stuff to new stuff, or encouraging them to prescribe existing drugs "off label" for conditions other than the ones they were originally approved to treat. All of those actions suggest pressure in the direction of faster adoption.

Also of note is the fact that disease is really common and tends to strike a broad cross section of people(some diseases more than others, of course. Some are virtually random, some have pretty strong demographic or genetic factors). Odds are very good that a fair number of key players in any big pharma/FDA sandbagging conspiracy(executives, officials, scientist who could blow the whistle) are either themselves sick, or have sick friends/family/pets, or both. An alarming number of people will screw over strangers for money, particularly if they don't have to see it happen, or feel personally responsible; and sociopaths would do the same to friends and family; but the payoff would have to be amazing for them to put themselves at serious risk. If it turns out that key players in medical research are using very different therapies than those that are generally recommended, it would be time to worry. As long as they and their families and friends are using basically the same techniques as everybody else, though, they have a pretty strong human incentive to do their jobs well.

Obviously, I'm not going to claim that there are never instances of sandbagging. I'm sure that there have been circumstances where, for whatever reason, an incentive existed, and I don't find it at all hard to believe that they went ahead and delayed. However, it seems quite unlikely that that is a major influence on medical development as a whole.

Re:Oh! No! Cure for cancer found.

[Anonymous Coward]

Not really. Cancer is one of the more costly ways to die, involving months of very expensive treatments that may or may not work. Its much better for your health insurance company if they can cure the cancer on the cheap and have you die of something less expensive later, like a heart attack or a a car crash.

Re:Expect the price to go up, up, up.

[KCWaldo]

It's a generic. Costs $4 for a month's dose. The price will not go up. They may come up with a new "version" that works better though.

More metformin news

[imgumbydamnit]

I read this item immediately after reading the A Genetic Fountain of Youth article in Technology Review. There on page two:

The new study also implicated the protein AMPK, a component of the TOR pathway even further downstream than S6K1, as a key potential drug target. The role of AMPK is especially intriguing because it is activated by metformin, a widely prescribed drug for treating type 2 diabetes. Withers says this means it may be possible in the next few years to design clinical trials that would test metformin's ability to prevent or treat age-related diseases.

Re:Expect the price to go up, up, up.

[MozeeToby]

http://www.accessmylibrary.com/coms2/summary_0286-11275848_ITM

Gee, thanks, I'll definately take that advice next time.

In 1987, the drug's creators had originally obtained a "methods" patent on using the combination of two generic vasodilators (hydralazine and isosorbide dinitrate) that seemed to have a pronounced beneficial effect in treating heart failure.

The methods patent, which expires in 2007, was not race-specific.

Soon thereafter the patent owners applied for a new race-specific methods patent to use the generic combination to treat heart failure in African-American patients.

If my knowledge of pharmecetical patents is so out of whack as to be foolish, that doesn't say a lot for the lawyers, judges, and patent inspectors involved in this case.