[GJM] Cheap, safe drug kills most cancers

[marguerite hampton]

 FYI 
Cheap, safe drug kills most cancers
11:58 17 January 2007 
>From New Scientist Print Edition. Subscribe and get 4 free issues. 
Andy Coghlan 
 http://www.newscientist.com/article/dn10971?DCMP=NLC-nletter&nsref=dn10971

What makes cancer cells different - and how to kill them
 
  
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.