Health Cures

DiChloroAcetate to Cure cancer

### DiChloroAcetate ( DCA )vs. Cancer: from

A Cheap and Simple Cure for Cancer? by Andy Coghlan ; New Scientist ( Wednesday, January 17, 2007 ) —

New Scientist has received an unprecedented amount of interest in this story from readers. If you would like up-to-date information on any plans for clinical trials of DCA in patients with cancer, or would like to donate towards a fund for such trials, please visit the site set up by the University of Alberta and the Alberta Cancer Board ( ). We will also follow events closely and will report any progress as it happens.

It is rare to find a drug that sweeps away decades of assumptions and reveals a radical approach to treating all forms of a disease. But a simple, small molecule called dichloroacetate (DCA) has done just that – and to that most dreaded of diseases: cancer.

The new findings ( ) might also force a rethink on what actually causes cells to turn cancerous in the first place. In 1930, biochemist Otto Warburg, proposed that cells turn cancerous through a fundamental change in the way they generate their energy. Normally, cells use specialised organelles called mitochondria to supply their energy. Cancer cells shift to a process called glycolysis which takes place in the main body of the cell. Glycolysis is an inefficient system of making energy which normal cells employ only when oxygen is in short supply, switching to mitochondrial energy production when oxygen levels increase.

Curiously, Warburg discovered that cancer cells continue to use glycolysis even when oxygen is plentiful. He called this the “Warburg effect”, and claimed it was common to all cancer cells. His ideas were dismissed and buried long ago, not least when another famous biochemist, Hans Krebs, said the Warburg effect was a symptom of cancer, not the primary cause. This scepticism was reinforced by the belief that cancer cells switch to glycolysis because their mitochondria are damaged and don’t work any more. Enter DCA, which has been used for years to treat people with mitochondrial disease. The drug boosts the ability of mitochondria to generate energy. When given to cancer cells it did the same: the cells switched from glycolysis to mitochondrial energy production. What’s more, functional mitochondria help cells recognise functional abnormalities and trigger cell death.

In tests, the DCA caused cancer cells to lose their “immortality” and die. When the drug was given to rats with human tumours, the tumours shrank. Warburg may have been right after all – glycolysis may be more than just a symptom of cancer. So why not rush straight into clinical trials with this drug? It is cheap, does not appear to affect normal cells, we know its side effects, and it should work on all cancers. There’s a hitch: dichloroacetate is an old drug and so cannot be patented. The upshot is that pharmaceutical companies can’t stop rivals making and selling it more cheaply, so it’s not worth their while to go to the huge expense of testing it in clinical trials. This is not a new problem. Many drugs are left on the shelf because companies cannot make lots of money from them. It has happened for diseases that affect mainly poor people, such as TB, although there are now an increasing number of initiatives to help deal with these cases. But cancer is historically a disease that chiefly afflicts the rich, and testing DCA will need a one-off effort. Drugs companies will be falling over themselves to find a patentable drug with similar action to DCA. Any of these that reach the market will be hugely expensive. It would be a scandal if a cheap alternative with such astonishing potential were not given a chance simply because it won’t turn a big enough profit.

# Mitochondria Activation Reduces Cancer, (January 21, 2007)

A small molecule activates suppressed mitochondria in cancer cells and the cells start acting normal.

January 16, 2007 – Edmonton – DCA is an odourless, colourless, inexpensive, relatively non-toxic, small molecule. And researchers at the University of Alberta believe it may soon be used as an effective treatment for many forms of cancer.One qualifier to the above statement: Whether dichloroacetate (DCA) would really be non-toxic when used in therapeutic doses against cancer remains to be seen. When used to treat a genetic disorder involving high lactic acid DCA caused peripheral neuropathy. DCA inhibits a kinase enzyme that deactivates an enzyme called pyruvate dehydrogenase (PDH) which is involved in mitochondrial metabolism (i.e, it is involved in sugar breakdown to make energy).

Dr. Evangelos Michelakis, a professor at the U of A Department of Medicine, has shown that dichloroacetate (DCA) causes regression in several cancers, including lung, breast and brain tumors. Michelakis and his colleagues, including post-doctoral fellow Dr. Sebastian Bonnet, have published the results of their research in the journal Cancer Cell.Many cancer cells do not break sugar down completely. They just do a step called glycolysis. They do not do a step called the Krebs cycle (aka the citric acid cycle or tricarboxylic acid cycle or TCA cycle) which extracts all the energy out of sugar molecules to make energy carrier molecules called NADH and ATP. This was first observed about cancer all the way back in the 1930s. Up until now the assumption to explain this was that cancer cells lost that ability. But this result suggests that not only do cancer cells suppress that ability but that suppression helps them grow uncontrollably.

Pyruvate dehydrogenase (PDH) synthesizes acetyl-CoA which is used in the first step of the TCA cycle in mitochondria. If DCA has either toxicity problems or problems with achieving sufficient doses that does not defeat this approach to anti-cancer drug development. The kinase that DCA blocks could become a target for drug development. A drug that would disable that kinase would likely activate mitochondria in cancer cells just like DCA does. I remember a scientist telling me decades ago that classic intermediary metabolism doesn’t get the attention it deserves because everyone was rushing into genetics. Many scientists decided that there was little of interest left to learn from studying the main pathways of energy metabolism. This result argues for his view. How can we get all the way to the year 2007 without noticing sooner the powerful results from a simple long known molecule? Michelakis decided the conventional wisdom on cancer and mitochondria might be wrong and decided to test it.

Until recently, researchers believed that cancer-affected mitochondria are permanently damaged and that this damage is the result, not the cause, of the cancer. But Michelakis, a cardiologist, questioned this belief and began testing DCA, which activates a critical mitochondrial enzyme, as a way to “revive” cancer-affected mitochondria. The results astounded him.

Michelakis and his colleagues found that DCA normalized the mitochondrial function in many cancers, showing that their function was actively suppressed by the cancer but was not permanently damaged by it.More importantly, they found that the normalization of mitochondrial function resulted in a significant decrease in tumor growth both in test tubes and in animal models. Also, they noted that DCA, unlike most currently used chemotherapies, did not have any effects on normal, non-cancerous tissues. No one single molecule is going to cure all cancers by itself. But combinations of compounds that each toxicity highly specific to cancer cells will certainly end up curing a great many cancers. Monoclonal antibodies targetted at cancers, anti-angiogenesis compounds that block blood vessel growth in cancers, gene therapies that activate in cancer cells and assorted other compounds such as DCA are going to cure many cancers when used in combination.

“I think DCA can be selective for cancer because it attacks a fundamental process in cancer development that is unique to cancer cells,” Michelakis said. “Cancer cells actively suppress their mitochondria, which alters their metabolism, and this appears to offer cancer cells a significant advantage in growth compared to normal cells, as well as protection from many standard chemotherapies. Because mitochondria regulate cell death – or apoptosis – cancer cells can thus achieve resistance to apoptosis, and this appears to be reversed by DCA.” The suppression of mitochondria might be a way for cancer cells to divide in low oxygen environments found deep in tumors lacking in sufficient vasculature. By turning on mitochondria in these cells their need for oygen is probably increased and that likely contributes to their death. This suggests that DCA might work well in combination with anti-angiogenesis drugs since the ability of anti-angiogenesis drugs to block blood vessel growth will decrease the amount of oxygen available to tumors and therefore make more cells in tumors susceptible to the effects of DCA.

DCA (aka Ceresine) has a big problem: It is not patentable and hence provides little incentive for commercial companies to raise money to fund clinical studies to develop it as an anti-cancer drug. People who are philosophically opposed to patents ought to take note of this. Furthermore, the DCA compound is not patented or owned by any pharmaceutical company, and, therefore, would likely be an inexpensive drug to administer, Michelakis added.However, as DCA is not patented, Michelakis is concerned that it may be difficult to find funding from private investors to test DCA in clinical trials. He is grateful for the support he has already received from publicly funded agencies, such as the Canadian Institutes for Health Research (CIHR), and he is hopeful such support will continue and allow him to conduct clinical trials of DCA on cancer patients.

If DCA is on the market in less regulated countries then maybe it’ll get tried out in human cancer patients under less restrictive regulatory regimes. DCA hasn’t been tried yet in humans against cancer.

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.People who have fatal diseases should be allowed to try anything as a treatment.


[ Complete Patent, PDF Format ]

Classification: – international: A61K31/19; A61P35/00; C12Q1/00; A61K31/185; A61P35/00; C12Q1/00; – European: G01N33/50D2B ; Application number: WO2006CA00548 20060411; Priority number(s): US20050669884P 20050411