Simpele stof tegen kanker.*

DCA of dichlooracetaat is een stof die volgens Canadese onderzoekers de groei van kankercellen onderdrukt zonder daarbij gezonde cellen aan te tasten. DCA wordt al tientallen jaren gebruikt om bepaalde metabolische problemen op te lossen. De stof is veilig en geeft nauwelijks bijwerkingen. De onderzoekers hebben DCA getest op menselijke kankercellen en kanker bij muizen, waar de stof werkzaam bleek te zijn. In gezonde cellen zorgen de mitochondria voor de energiebehoefte van de cel. Bij abnormale celgroei zorgt diezelfde mitochondria voor een versnelde dood van de cel. In kankercellen worden de mitochondria buiten spel gezet en zorgen suikers in een proces wat glycolyse heet voor de energievoorziening en een snelle groei. Door het buiten spel zetten van de mitochondria wordt een kankercel eigenlijk onsterfelijk. DCA zorgt nu ervoor, althans tijdens deze tests, dat de mitochondria weer geactiveerd worden en de kankercel doet afsterven. De onderzoekers van de Universiteit van Alberta adviseren het gebruik van dichlooracetaat (DCA) voor de behandeling van kanker bij mensen nog niet, omdat er nog geen klinische onderzoeken hebben plaatsgevonden naar de behandeling van kanker bij mensen met DCA. Doordat geen patent mogelijk is op deze stof dienen de onderzoekers de kosten voor deze uitgebreide klinische onderzoeken (trials) zelf op te brengen. Daarvoor wordt iedereen om een bijdrage gevraagd. Kijk daarvoor hier. Het grote voordeel is wel dat als de testen goed uitvallen er een goedkoop en veilig middel zou kunnen zijn tegen kanker.

Cheap, safe drug kills most cancers

What makes cancer cells different - and how to kill them

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 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.

Meer informatie: http://www.depmed.ualberta.ca/dca/faq.pdf (Febr. 2007) 

 

 

 

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