23 January 2007
From New Scientist Print Edition
Cheap, safe drug kills most cancers
by Andy Coghlan
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.
