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newscientist.com reports that researchers at the University of Alberta has discovered that a cheap, relatively safe drug kills most cancers. Chances are most pharmaceutical companies will pass up the opportunity to do further research since little profit could be made from the drug, which means that most research will probably be done by Universities, financed by both private and public funding.



# Updated 16:37 12 December 2007
# NewScientist.com news service
# Andy Coghlan

It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their “immortality”. The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe.

It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

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.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis’s experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died (Cancer Cell, DOI: 10.1016/j.ccr.2006.10.020).

Michelakis suggests that the switch to glycolysis as an energy source occurs when cells in the middle of an abnormal but benign lump don’t get enough oxygen for their mitochondria to work properly (see diagram). In order to survive, they switch off their mitochondria and start producing energy through glycolysis.

Crucially, though, mitochondria do another job in cells: they activate apoptosis, the process by which abnormal cells self-destruct. When cells switch mitochondria off, they become “immortal”, outliving other cells in the tumour and so becoming dominant. Once reawakened by DCA, mitochondria reactivate apoptosis and order the abnormal cells to die.

“The results are intriguing because they point to a critical role that mitochondria play:

they impart a unique trait to cancer cells that can be exploited for cancer therapy,” says Dario Altieri, director of the University of Massachusetts Cancer Center in Worcester.

The phenomenon might also explain how secondary cancers form. Glycolysis generates lactic acid, which can break down the collagen matrix holding cells together. This means abnormal cells can be released and float to other parts of the body, where they seed new tumours.

DCA can cause pain, numbness and gait disturbances in some patients, but this may be a price worth paying if it turns out to be effective against all cancers. The next step is to run clinical trials of DCA in people with cancer. These may have to be funded by charities, universities and governments: pharmaceutical companies are unlikely to pay because they can’t make money on unpatented medicines. The pay-off is that if DCA does work, it will be easy to manufacture and dirt cheap.

Paul Clarke, a cancer cell biologist at the University of Dundee in the UK, says the findings challenge the current assumption that mutations, not metabolism, spark off cancers. “The question is: which comes first?” he says.

Comments

( 3 comments — Leave a comment )
agoraphiliac
Sep. 20th, 2008 01:06 pm (UTC)
It worked because "reawakened the mitochondria in cancer cells." That's awesome.

It's like that children's book by Madeleine L'Engle, uh, a Something in Time. A Wrinkle in Time. The plot hinged on traveling into a dying person's cell and persuading their mitochondria to do their job. As I recall it was conservative; the mitochondria were manically partying instead of, uh, doing their moral duty and reproducing I guess. So, probably not so much a favorite childhood book, or a book you'd want to go read now.
eriktrips
Sep. 20th, 2008 08:43 pm (UTC)
yeah I can't find any really recent articles on it but I assume they are still researching it in Alberta; the research page is still up.

I really like the idea of being able to persuade mitochondria to do something even if it is in service of a puritan work ethic. but yeah, probably won't read it. knowing that the story exists is enough to be amusing without having to be annoyed as well.
yangming
Sep. 21st, 2008 08:57 pm (UTC)
Wow, that's cool. There's all kinds of switches in our bodies like that. I've been thinking a lot about the mitochondria and I think they are what Chinese medicine calls Qi. When you increase activity they increase in abundance. And they hold the knowledge of our ancestry since they aren't involved or can mutate during sexual reproduction...a translation of the Jing of Daoists.

This might interest you...one of the researchers who found the endogenous opiods has also found the receptor proteins for neurotransmitters all over the body rather than just in the brain. That confirms what we all sense...that our bodies have memories. I can't find the research though, since I don't have access to journal article databases anymore...oh maybe I can find it through Merritt college...
( 3 comments — Leave a comment )

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