Cheap, Safe Drug Kills Most Cancers

[JCarvingblock]

Cheap, safe drug kills most cancers

* 20 January 2007
* NewScientist.com news service
* Andy Coghlan

http://www.newscientist.com/channel/health/mg19325874.700-cheap-safe-drug-kills-most-cancers.html

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.

From issue 2587 of New Scientist magazine, 20 January 2007, page 13

[GoldWampum]

Interesting article. Worth following the story.

[Tn...Andy]

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.

This would also corelate to the use of the suppliment Co-Q10, which is another natural substance not patentable by drug companies. Though generally thought to be a big help in the treatment of congestive heart failure problems, it may also play a role in cancer treatment.

"CoQ10 is found in every cell in the body. Animal species have exhibited a direct correlation between CoQ10 levels and longevity.[1] The use of statin drugs produces significant falls in CoQ blood levels which may be the reason for the rising incidence of heart failure as statin drugs are widely used in the U.S. to lower cholesterol. Administration of CoQ10 improves energy output by the mitochondria of the cell. "

Dr. Folkers followed the course of 6 patients, who had cancer, who were taking CoQ10 for congestive heart failure until 1993. Four of them had lung cancer and 2 had breast cancer. All 6 experienced remissions of cancer thought to be due to CoQ10 therapy. Dr. Folkers recommended the use of 500 mg. of CoQ daily in patients with malignancies.

Read the whole article:

http://www.newswithviews.com/Howenstine/james2.htm


Wife and I have been on a regimen of Co-Q10 for years now, along with other suppliments due to history of heart failure on both sides of our family. Be interesting to see if it also helps prevent cancer. Going in next week for my first routine "roto-rooter" inspection, betting they find no cancerous polyps.

[GoldWampum]

The Why Files -- whyfiles.org
18 JANUARY 2007

Promoting cancer suicide?
For more than 70 years, scientists have known that cancer affects mitochondria, the tiny structures that process energy inside cells. Mitochondria normally get their power from oxidizing the sugar glucose, but in tumors, the mitochondria quit functioning, and tumor cells resort to breaking down glucose without oxygen.

Dichloroacetate (DCA) is a simple molecule with two oxygens, two chlorines, and two carbons. DCA has been used to treat a rare illness in mitochondria, which process energy inside cells. Unlike many new cancer drugs, you can take DCA by mouth. Courtesy University of Alberta

Although most scientists thought mitochondrial malfunction was a result, not a cause, of cancer, it now seems that it could be integral to the disease process.

This matters for two reasons. First, mitochondria are critical triggers of a cancer-killing mechanism called programmed cell death, AKA apoptosis or cellular suicide. In a healthy body, tumor cells should commit suicide, not grow.

And second, the new understanding could reveal new targets for cancer drugs.

Managing mitochondrial malfunction
These implications are the background for a new study from the University of Alberta, showing that the cancer-induced decline in mitochondria can be reversed. Writing in Cancer Cell, associate professor of medicine Evangelos Michelakis and colleagues describe experiments performed on human cancer cells -- in lab dishes and in experimental animals.

Under normal conditions, mitochondria "burn" -- oxidize -- glucose to make usable energy for the cell. When oxygen is absent, cells resort to glycolysis, a breakdown process that liberates lactic acid. Lactic acid helps cause muscle cramping during exercise, but it can also help cancer cells move in the body -- to metastasize.

Scientists have long known that mitochondria play a role in cancer, says Michelakis. When the mitochondria quit producing energy, cells cope by breaking down glucose outside the mitochondria. Because this process is inefficient, it needs abnormal amounts of glucose, which happens to be why cancer cells can be detected with PET scans. Positron emission tomography measures glucose usage, Michelakis says. "PET detects cancer because tumors have shut off the mitochondria, and have to rely on less efficient means of generating energy. The cancer cells are drinking glucose like crazy, and this distinguishes them from normal cells."

As evidence mounted for a major role of mitochondria in cancer, Michelakis, a specialist in cardiology who specializes in energy metabolism inside cells, Sebastian Bonnet and their colleagues began to wonder if they could restore the mitochondria and thereby affect cancer. They focused on dichloroacetate (DCA), a drug that pushes glucose metabolism back toward normal oxidation, and is sometimes used to treat mitochondrial problems.


After three weeks, the tumor is much smaller in the DCA-treated rat than in the control rat -- showing either shrinkage or slower growth. Courtesy University of Alberta

Cancer: shrink thyself!
When the researchers injected human lung cancer cells into rats, tumors shrank significantly in animals that got DCA, compared to the animals that did not get the drug. Tests showed that apoptosis was operating in the tumors in these DCA-treated animals, but not in the control animals.

The drug DCA reduces tumors but does not eliminate them. Green: DCA was given when the rats are injected with tumor cells. Red: DCA was given two weeks after tumor injection. Blue: Control animals got tumor cells, but not DCA. Data from Bonnet et al (see below).

DCA affected tumors when it was given either before or after the cancer cells were injected, indicating that it may have a role in preventing and curing cancer.

Biochemical tests showed that mitochondria in the DCA-treated cancer cells were releasing compounds that stimulate apoptosis -- cellular suicide. Many cancer drugs work through apoptosis, but cancer cells often resist committing suicide, at least partly because the shut-down mitochondria cannot start the suicide processes. The results support a relatively new line of studies showing that mitochondria play a major role in regulating apoptosis.

While this treatment has not been tested in people or any animal except rats, DCA has a number of theoretical advantages over expensive, highly toxic cancer treatments: It is not patented, and therefore cheap. It is a small molecule that can be taken orally. And more than 30 years of medical use has revealed minimal side effects.

Programmed cell death with DCA

DCA-treated rats had smaller tumors due to an increase in programmed cell death, as measured by TUNEL (don't even ask what that stands for!) and a decrease in proliferation, which is part of metastasis. Data from Bonnet et al (see below).

Perhaps the most intriguing aspect of the discovery is this: Damage to mitochondria is widespread in many types of cancer, Michelakis says, indicating that DCA could have broad use -- if it works as well in people as in rats. The next step, he adds, is to start a small trial among patients with the three cancers already tested (glioblastoma, a type of brain cancer; non-small-cell lung cancer; and breast cancer). The details of upcoming trials "will depend on funding," he adds. Because DCA, cannot be patented, "industry is not particularly interested" in funding research.

But because DCA is already on the market, the first trial could begin in a few months.

Breast cancer cell. Photo: NIH, courtesy National Cancer Institute.

At this point, Michelakis is enthusiastic that energy metabolism may point to ways to overcome cancer. "DCA attacks a fundamental and unique property of cancer. It puts the mitochondria back in the normal condition, and because the mitochondria can control cell death, that also comes back into the picture."

One possible therapeutic approach, he says, would use DCA to sensitize tumor cells to apoptosis, and then attack the cancer with standard chemotherapy drugs. Ideally, lower doses of the highly toxic chemotherapy drugs would be effective once tumor cells lose their immunity to programmed cell death.

— David Tenenbaum


Bibliography
• Bonnet et al., A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth, Cancer Cell (2007), doi:10.1016/j.ccr.2006.10.020

Related Why Files
• Apoptosis, fetal alcohol syndrome and anesthetics.
• Skin cancer






See also...
Lung Cancer Screening: Good Idea?
Africa: Scientific Advances
Skin Cancer Today


Extra:
Big climate report: Humans "very likely" caused global warming.
Stardust mission comet dust analyzed
Ex-football player's suicide due to brain damage



More...

Education
Archives


Cool Science Images

A Spot on the Sun

Interactives

Virtual Science!

Teacher Activities

Nuts 'n Bolts
Talk to us
Store
Join mailing list
About this site
About the team
RSS
©2007, University of Wisconsin, Board of Regents.

http://whyfiles.org/shorties/225cancer_drug/


--------------------------------------------------------------------------------

DCA RESEARCH INFORMATION

--------------------------------------------------------------------------------

MEDIA
Contacts and Photographs
Dr Evangelos Michelakis
Department of Medicine, University of Alberta

Frequently Asked Questions



Updated January 23, 2007


--------------------------------------------------------------------------------

Investigators at the University of Alberta have recently reported that a drug previously used in humans for the treatment of rare disorders of metabolism is also able to cause tumor regression in a number of human cancers growing in animals. This drug, dichloroacetate (DCA), appears to suppress the growth of cancer cells without affecting normal cells, suggesting that it might not have the dramatic side effects of standard chemotherapies.

At this point, the University of Alberta, the Alberta Cancer Board and Capital Health do not condone or advise the use of dichloroacetate (DCA) in human beings for the treatment of cancer since no human beings have gone through clinical trials using DCA to treat cancer. However, the University of Alberta and the Alberta Cancer Board are committed to performing clinical trials in the immediate future in consultation with regulatory agencies such as Health Canada. We believe that because DCA has been used on human beings in Phase 1 and Phase 2 trials of metabolic diseases, the cancer clinical trials timeline for our research will be much shorter than usual.

This website will be updated frequently to reflect progress in our efforts.





If you wish to be added to our mailing list, please enter your e-mail address below and we will keep you informed when important new information is added to this site.






INTERVIEWS WITH DR. MICHELAKIS




CTV National News


Global Edmonton News


--------------------------------------------------------------------------------

OTHER LINKS OF INTEREST



Newsweek Article
January 23, 2007


Globe and Mail Article
January 17, 2007


New Scientist Article
January 20, 2007


U of A ExpressNews Article
January 16, 2007


Economist.com Article
January 18, 2007


National Post Article
January 17, 2007


Cancer Cell Article
January 2007







--------------------------------------------------------------------------------


--------------------------------------------------------------------------------


--------------------------------------------------------------------------------


--------------------------------------------------------------------------------


--------------------------------------------------------------------------------



--------------------------------------------------------------------------------

DONATIONS

To mail or drop off your donation:

CLICK HERE TO PRINT THE DONATION FORM
(Adobe Acrobat PDF)
To make your donation on-line:

CLICK HERE TO MAKE A DONATION ONLINE
When prompted, select DCA Cancer Research Fund


Donations can be mailed or dropped off at:

Faculty of Medicine & Dentistry
Room 2J1
Walter C Mackenzie Health Sciences Centre
University of Alberta
Edmonton, Canada T6G 2R7




Please note on your cheques that you would like your donations to support Dr. Michelakis’ cancer research.



If you would like to speak to someone about making a gift please contact:


Holli Bjerland, Sr. Development Officer
University of Alberta, Department of Medicine
2F1.26 Walter C Mackenzie Health Sciences Centre
Edmonton, AB CANADA T5G 2R7
Tel: (780) 407-6524
Fax: (780) 407-3340
E-mail: holli.bjerland@ualberta.ca

http://www.depmed.ualberta.ca/dca/

Last updated Wednesday, January 31, 2007

[Tn...Andy]

Good info, thanks GW.