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 ( http://www.depmed.ualberta.ca/dca ). We
will also follow events closely and will report any progress as it
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
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
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
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
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.
(January 21, 2007)
Mitochondria Activation Reduces Cancer
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
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
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
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.
A METHOD OF TREATING CANCER USING
( 10-19-2006 )
[ PDF ]
MICHELAKIS EVANGELOS (CA); ARCHER STEPHEN (CA)
Applicant: UNIV ALBERTA (CA); MICHELAKIS EVANGELOS (CA); ARCHER
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
Environmental Health Perspectives 106 (Suppl. 4):
989-994 (August 1998)
Peter Stackpoole, et al.: Clinical Pharmacology and
Toxicology of Dichloroacetate
[ PDF ]
DCA v CANCER
Cheap, safe drug kills most cancers... However, Michelakis's
experiments prove this is not the case, because DCA reawakened
the mitochondria in cancer cells. The cells then withered and
FuturePundit: Mitochondria Activation Reduces Cancer
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.
www.futurepundit.com/archives/004028.html - 17k
mitochondria | Science Buzz
When cells switch mitochondria off, they become “immortal",
outliving other cells in the tumour and so becoming dominant.
Once reawakened by DCA, ...
buzz.smm.org/buzz/buzz_tags/mitochondria - 15k
Science Buzz - mitochondria
Once reawakened by DCA, mitochondria reactivate apoptosis and
order the abnormal cells to die. But perhaps the best thing
about this ...
buzz.smm.org/buzz/taxonomy/term/2019/0/feed - 4k
DCA: A cheap, safe, effective “cure" for cancer? at Fresh.
Because mitochondria regulate cell death–or apoptosis–cancer
cells can thus achieve resistance to apoptosis, and this appears
to be reversed by DCA." ...
Small molecule offers big hope against cancer - ExpressNews ...
Scientists and doctors have used DCA for decades to treat
children with inborn errors of metabolism due to mitochondrial
diseases. Mitochondria, the energy ...
www.expressnews.ualberta.ca/article.cfm?id=8153 - 22k
The Why Files | Small molecule could be big cancer fighter
Biochemical tests showed that mitochondria in the DCA-treated
cancer cells were releasing compounds that stimulate apoptosis
-- cellular suicide. ...
whyfiles.org/shorties/225cancer_drug/ - 17k
However, Michelakis’s experiments prove this is not the case,
because DCA reawakened the mitochondria in cancer cells. The
cells then withered and died ...
bittertizer.wordpress.com/ - 24k
ScienceDaily: Small Molecule Offers Big Hope Against Cancer
Because mitochondria regulate cell death--or apoptosis--cancer
cells can thus achieve resistance to apoptosis, and this appears
to be reversed by DCA." ...
www.sciencedaily.com/releases/2007/01/070116134001.htm - 99k
Once reawakened by DCA, mitochondria reactivate apoptosis and
order the abnormal cells to die. “The results are intriguing
because they point to a critical ...
www.tedkarol.com/blog/index.xml - 10
Thursday, March 29, 2007
Cancer Pharmacy for the Desperate and
Linda Geddes, Biomedical editor
Almost two years ago my aunt died from ovarian cancer. At age
53, she was younger than my mother and, the last time I saw her,
I remember her producing a pile of computer print-outs of
alternative cancer therapies she had read about on the internet.
She was desperate, and she wanted my advice on whether the
science behind their claims was robust or not. After examining
the literature, it was with great sadness that I told her that,
in my opinion, their claims were unfounded.
Pouring cold water on someone’s hopes is a terrible thing. In
the case of DCA, I have to say there are at least some grounds
for excitement. Lab studies have shown that it can kill cancer
cells by reactivating mitochondria, which will then recognise a
cell as cancerous and destroy it. But until we see whether this
mechanism applies to cells in the human body it is impossible to
know whether it will work in human cancer.
We also have no idea of the doses that could produce this
effect; of their side effects in cancer patients, or about
whether DCA interacts with existing cancer medications. DCA is
not a harmless drug – as Lawrence Burgh’s example illustrates,
it can have side effects. Fortunately, Burgh is a physician
whose oncologist was aware that he was taking DCA. He was taking
supplements to try and reduce side effects, and at the first
sign of trouble, he stopped taking it.
Not everyone who is experimenting with DCA is so cautious.
Self-medicating with DCA could cause nerve or liver damage, and
perhaps even death. People with terminal cancer may feel that
they have nothing to lose – but there may be a different option.
Statistically speaking, if a cancer drug has passed initial
safety tests in phase 1 clinical trials, it has a one in 20
chance of being approved. If it has passed phase 2 trials (the
stage before large scale trials in patients with the disease) it
has a one in 5 chance of being approved. Yet doctors are
struggling to recruit patients into these trials. In the US,
fewer than 5% of adult cancer patients are enrolled. True, not
everyone can take part in clinical trials because they have
other physical ailments, their insurance companies won’t cover
them, or because they live too far away from trial centres. But
it seems at least worth trying, before opting for the
ultra-gamble of DCA.
Sadly, many of the posts I came across while researching the
DCA site, expressed a feeling that their doctors didn’t care –
that they were made to feel like “dead men walking". I’m sure
that most doctors do their utmost to listen to their patients
concerns, but for those who fall through the net, it should be
noted that website communities seem to be filling a gap in
providing at least some of the comfort, support, and hope that
impersonal hospital visits may lack.
When this drives people to campaign for a drug like DCA to be
put through clinical trials, or to push doctors to try the
latest approved drugs, this can be a great thing. But people
should treat what they read on the internet with care. There is
a risk that these forums could push an already vulnerable person
to make their shortened life even more painful.
So what is the answer in a situation like this? Should patients
have the ultimate say in how they choose to treat their own
bodies; or should these most vulnerable of people be protected
from the exploitative promises of untried therapies?
Illegal 'cancer drug' website shut down
27 July 2007
NewScientist.com news service
by Linda Geddesdca
"Is DCA worth trying? We absolutely think so," proclaimed a
website promoting the laboratory chemical sodium dichloroacetate
(DCA) as a treatment for cancer earlier this year.
The US Food and Drug Administration (FDA) clearly did not
agree. Last week it visited the site's owners and told them to
stop making and selling DCA from a sister website, or face
Jim Tassano of Sonora, California, claims to have sold DCA to
more than 2000 people, with no reports of serious side effects,
via his website www.buydca.com.
However, on the 17 July he posted the following message on the
site. "Two agents from the FDA visited us today and ordered that
we stop making and selling DCA. Unfortunately, the site
www.buydca.com will be shut down. It is against US government
law to sell substances with the suggestion that they are cancer
treatments unless they are approved by the FDA. DCA can still be
obtained from pharmacies with a prescription and from chemical
The FDA confirmed that agents from their Office of Criminal
Investigations had visited Tassano, but declined to comment
In an interview with New Scientist, Tassano told us: "We've
seen cancers where it doesn't seem to respond at all [to DCA],
but a lot of people have reported improvements in their
"I'm disappointed [that the FDA has shut the website down], but
not surprised. It is an unapproved cancer treatment and we have
become very high profile. I guess the pressure has got to be too
much for the FDA," he said.
Tassano continues to host discussions on the supposed virtues
of the chemical, which has not yet undergone human trials as a
cancer therapy, on his original site www.thedcasite.com.
Researchers studying DCA as a potential cancer drug welcomed
the FDA's action. "The FDA is doing the absolutely right thing
to help protect vulnerable cancer patients from the unregulated
use of a drug that should be studied in properly designed
clinical studies," says Chi Van Dang at Johns Hopkins University
Medical School in Baltimore, Maryland, US.
Kate Law, Cancer Research UK's clinical trial director, agrees:
"Reports of people buying personal supplies of DCA from sources
such as the internet were very worrying."
"It is important that all new treatments are carefully
investigated to make sure they are effective and safe for use in
patients. DCA is no exception, so we are pleased that the FDA
has taken the decisive action to limit the sale of DCA over the
internet," she says.
Clinical trials of DCA are expected to take place in the near
future. Evangelos Michelakis of the University of Alberta in
Edmonton has just resubmitted protocols to Health Canada, and
hopes to gain approval to for a safety trial of DCA in human
cancer patients in the coming weeks.
Meanwhile, Van Dang has just received notice of funding to
carry out additional studies of DCA in animals with cancer, with
the intention of conducting clinical trials in lymphoma patients
within three years.