Harvard Scientists Aim To Stop Cancer In Its Tracks

Shuntros writes "BBC News is reporting progress from scientists at Harvard Medical School towards strangling the growth of cancer cells. By starving cells of a certain type of enzyme, growth essentially ceases. 'The fact that proliferating cancer are able to consume glucose at a much higher rate than normal cells was first discovered by the German Nobel prize-winning chemist Otto Warburg more than 75 years ago. He also showed that the amount of glucose the cells needed to keep their vital signs ticking over was minimal, allowing them grow and divide at the prodigious rate usually associated with foetal cells.' Certainly not a cure by any stretch of the imagination, but putting the brakes on cancer growth in this way is very much akin to the revolution that was AZT."

Still need an inhibitor

[Btarlinian]

While this discovery is of great importance, we still need to find an inhibitor for this enzyme that will not also inhibit normal pyruvate kinases. BTW, if anyone is interested in reading more about the discovery, Harvard Medical School has a more detailed press release [harvard.edu] and the two related articles in Nature can be found here (protein structure) [nih.gov] and here (relationship to cancer) [nih.gov]. We haven't gotten to AZT yet, but this is a pretty large step towards finding a sort of "magic bullet" for tumors. At the very least, it's a common weakness most cancerous cells share.

Promising result

[Armakuni]

Apparently, the major problem with cancer is that it isnt't just one disease, it's a whole myriad of conditions with one common characteristic - uncontrolled cell division. Finding one factor that brakes or halts growth in all cancers is a bit of a holy grail for scientists, and this enzyme seems to have at least some of the hallmarks.

Re:I saw a documentary on this

[alzoron]

actually, http://science.slashdot.org/article.pl?sid=08/03/03/189243 [slashdot.org] is what you're looking for.

This is a completely different approach, it only slows cancer using a drug to restrict the presence of a certain enzyme. In I Am Legend they used a retrovirus to control the cancer. (They used a modified version of measles which technically is a paramyxovirus, not a retrovirus

Re:Wonderful editorial work

[Btarlinian]

The editors missed the most important fact. This is the enzyme which is actually inhibited by DiChloroAcetic Acid which was recently reported as the Wonder Drug by other groups of scientists.

DCA [wikipedia.org] inhibits pyruvate kinases, not just the M2 variety discovered and reported in the Nature article. That's why its side effects are so problematic. After all, normal cells do undergo glycolysis (the Krebs cycle, i.e., aerobic respiration, cannot continue without the products of glycolysis), it's just not as large a fraction of their energy source as tumors. The activity of DCA is simply based upon the Warburg effect, not on the inhibition of this specific variety of pyruvate kinase.

Re:Really disappointed in our Cancer researchers.

[pauljlucas]

Gene therapy = failure.

You're not keeping up. Chronic Myeloid Leukemia has been cured by gene therapy [pbs.org]. The problem, as another poster pointed out, is that "cancer" is a broad label for many thousands of individual diseases. A particular gene therapy targets only one kind of cancer.

Re:Low Carb? No Really.

[siddster]

And he would be wrong. The link between a high carbohydrate diet and cancer is tenuous at best. Not only that but high-fat diets have been implicated in raising the risk of some cancers. (Specifically prostate cancer) You could try reading these research studies. Long story short, cancer is a bunch of incredibly heterogenuous disorders and tumour growth is driven by totally different set of chemicals and enzymes depending on the type of cancer a patient has.

E. Giovannucci, E.B. Rimm and G.A. Colditz et al., A prospective study of dietary fat and risk of prostate cancer, J Natl Cancer Inst 85 (1993), pp. 1571-1579.

P.H. Gann, C.H. Hennekens and F.M. Sacks et al., Prospective study of plasma fatty acids and risk of prostate cancer, J Natl Cancer Inst 86 (1994), pp. 281-286

D.A. Snowdon, R.L. Phillips and W. Choi, Diet, obesity, and risk of fatal prostate cancer, Am J Epidemiol 120 (1984), pp. 244-250

A.W. Hsing, L. Tsao and S.S. Devesa, International trends and patterns of prostate cancer incidence and mortality, Int J Cancer 85 (2000), pp. 60-67

Re:Promising result

[protobion]

To extend that point actually, cancer is is characterized by a lot of secondary mutations in so called oncogenes, the most prevalent of these are now quite well characterized. This particular article talks about the metabolic side of cancer, but the genetic component still exists, and unlike the metabolic state, is more likely to be inherited in subsequent generations of cancer cells. Cancer is often a self-propagating cycle at the cellular level and so permit me the cynicism if I am a tad cautious of PKM2 being the crucial target that stops it all.

Re:Wonderful editorial work

[hedwards]

however, approval for use as a 'dietary supplement' is far, far, far more lax. After all, stevia was approved as a 'dietary supplement' years and years before coke/cargil got in on the game...

sold as a real medicine, not likely, but someone could probably get it approved as a dietary supplement with some 'fancy trade mark name' in however long it takes to get the paperwork through... and the websites touting it's use for blah blah blah, and how much to use etc...

Definitely not, it doesn't qualify as a supplement under the FDA's definition. Stevia definitely does qualify as a supplement. The only part that is even the smallest bit hazy is that last rule, and even that is pretty solid.

OTOH, there's no way at this point that DCA isn't going to run afoul of the definition at this point. It also isn't meant to supplement a person's diet. It just doesn't conform to the definition that the FDA uses for deciding whether or not a substance is a supplement.

http://www.cfsan.fda.gov/~dms/dietsupp.html [fda.gov] has more information on that.

Re:Low Carb? No Really.

[tie_guy_matt]

Taubes based his observation on the accounts of western trained doctors who set up hospitals to treat the members of these tribes. So according to his book the answer is: quiet frequently and quiet a lot of records.

However, many of those accounts were from doctors practicing in the late 1800's and early 1900's which explains why other people may ignore these accounts. It is likely though that even those old doctors would know some forms of cancer when they saw them and yet there are accounts of doctors spending years at hospitals servicing thousands of tribal members and yet the doctors would only see one or two cases of cancer (or in some cases none at all) during the entire time they were there, or until the tribes got more money and became westernized or switched to a more western diet. They would then go to a hospital in Philadelphia (as one example he mentioned) and see hundreds or thousands of cases of cancer from people of all races (discounting the idea that these tribes are genetically predisposed to not get cancer or that doctors at the time didn't know many forms of cancer when they saw it.)

All I can say is, even if you are skeptical you should read the book.

Re:Wonderful editorial work

[kesuki]

well TFA fails to mention that DCA is Already an approved drug.
"DCA has been used historically to treat patients with lactic acidosis, and therefore could arguably enter phase 2 trials in patients with cancer"

no need to do phase 1 trials then the cost goes DOWN considerably. and consider that any generic drugs have to get through hurdles with the FDA as well... well, there could well be money to be made in the states...

and although it's not 'official' a pair of plucky Canadians have been using DCA with 'reported success' (not scientific of course) and Canada didn't bar them from doing this either.

Warburg's other effect

[DynaSoar]

Warburg got two Nobels (IIRC, 1928 and 1931), in part by studying the role of oxygen in cell metabolism. Cancer cells use an anaerobic mechanism for metabolism. Flooding them with oxygen disrupts this anaerobic activity. This may account for at least some of the glucose effect in TFA. This can be accomplished using hyperbaric oxygen (high O2 content greater than 1 atmosphere's partial pressure).

It can also be done using superoxides (ozone, which produces hydrogen peroxide in the body, or H2O2 itself). Superoxide production is a normal part of the immune system, and cancer cells don't increase their SOD production proportionally with their growth rate. This is because the superoxides work on mitochondria, where metabolism occurs. The main cell is what's cancerous, not the mitochondria.

Another way to increase H2O2 in the body is to inhibit the enzyme that protects cells from high levels of H2O2, superoxide dismutase (SOD), allowing natural or infused levels of the substance to increase. Penicillin is one such SOD inhibitor, and other antibiotics are being tried. The effects are variable but generally positive. This can be facilitated by including manganese, selenium or zinc, around which the SOD builds itself, explaining the role of minerals containing these to be helpful in fighting infections.

Yes, the increased H2O2 levels can be harmful to cells, or else the body wouldn't have a mechanism to keep it in check. This is the role antioxidants play. Excessive H2O2 is an earmark of autoimmune diseases. There is an optimum level for normal cells. But cancer cells are much more sensitive, and a little damage due to superoxides is preferred over a lot of damage due to cancer.

I found some of the above information while researching my dissertation. It was based on inhibiting another oxygen scavenger, monoamine oxidase (MAO). The MAO inhibitor I looked at is trimethyl naphthoquinone (TMN), and this substance can protect the body from at least one autoimmune disease, Parkinson's. It is ironic then that one common source of TMN is in smoking tobacco. An anti-carcinogen effect isn't seen in smoking (though it may in fact occur) because of the other chemicals in smoking which are carcinogenic to an extent orders of magnitude greater than TMN's. Its MAO inhibition plateaus at low doses whereas the carcinogens don't, so getting TMN is better accomplished other ways. This, and other MAO inhibitors might be helpful in fighting cancer. These are not being widely tested, but the little research so far (mostly in other natural products) is showing some anti-carcinogen effect. SOD inhibition is probably much more effective than MAO inhibition, however the MAO inhibitor effect supports the hypothesized role of oxygen via a second if less effective mechanism.

Re:Low Carb? No Really.

[siddster]

Good question and in fact it appears that diabetics have a lower incidence of prostate cancers in epidemiological studies. A note about carbohydrate and fat metabolism.

Carb metabolism = glycolysis >> TCA cycle / Krebs cycle >> Electron transport chain
Lipid (Fat) metabolism = beta oxidation >> Krebs cycle >> Electron transport chain

Since the lipid molecules have longer carbon chains, the by-products of beta-oxidation can enter the Krebs cycle several times over which gives fat the ATP advantage.

Re:Wonderful editorial work

[glwtta]

no need to do phase 1 trials then the cost goes DOWN considerably

Phase I trials are actually only a tiny portion of the cost. Typically they involve giving the drug to a couple dozen or so terminal patients to asses the safety/side effects, find the tolerable dose, etc. It's kind of a touchy area, since no matter how many animal trials you do, you can never really be sure that the drug won't have severe side effects, or even kill a human outright (that one's unlikely, but you won't know until you give it to humans).

So the whole thing will usually run only a couple million dollars. It's when you get to phase II and III, with hundreds and thousands of patients, that the real costs come into the picture.

Re:Promising result

[cmaley]

To further extend the point: While it is true that there are many types of cancer with different genetics, there is a further fundamental problem in cancer therapeutics. Tumors are composed of billions to trillions of cells with tens of thousands of mutations (by some measurements). Clinical experience shows that when you apply a drug to such a genetically diverse population, you often kill most of the cells but select for resistance mutations. Thus the tumor grows back from the remaining resistant cells and the patient relapses. This is one of the major reasons we have not been able to cure cancer. These results, while potentially important, will not solve that basic problem in cancer therapy. They will select for their own form of resistance mutations.

Re:Promising result

[chooks]

You are right -- for example, CHOP therapy for Hodgkin's disease. Wikipedia has a list of other chemo regimens [wikipedia.org]. Combination therapy is usually much better for a number of reasons, among them being better outcomes.

Re:There already exists a cancer cure...

[RonBurk]

I call BS. No less authority than MD Anderson (#1 cancer facility in U.S.) has been studying curcumin for years (which the woman points out is how she found out about it). MD Anderson has not found it to be "a cure for cancer" so far. MD Anderson studies far outweigh the data point of "a friend of my mother's". I can find nothing in her blog that indicates she had "metastasized" cancer. Please don't go around telling people she cured metastasized cancer with curcumin; you may give false hope to, for example, someone with metastasized breast cancer, a disease that has a nearly perfect kill rate at Stage IV.

Cancers differ based on the type of cell that originally became cancerous, just like car wrecks differ depending on the type of vehicle. She has multiple myeloma, and some varieties of MM are so indolent that doctors recommend no treatment. If your doctor recommends "let's wait and see if it actually gets worse", then knock yourself out with curcumin.

This is not a knock against curcumin, which may turn out to be a useful anti-cancer agent, and I certainly put it my wife's adjuvant therapy (amongst a *great* many other substances) to try to prevent metastasis. It's a knock against claiming a cure for cancer exists and is cheap and is just ignored because of financial reasons. Before you do that, please spend a few years studying cancer and walking the cancer wards. If you don't have great respect for how far the problem of cancer thus far exceeds our intelligence, then you don't understand cancer.

Ditto for IP6. If you get cancer and want to forgo treatment in favor of phytochemicals, despite the clear evidence that your body has allowed a cancer to grow unfettered and needs some major help, then good luck with that and let me know how that works out for ya. But don't tell other people to do that. Some desperate fool might think you know what you're talking about.