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DCA has been tested in a small trial

The controversial drug DCA (dichloroacetate) is in the headlines again, after researchers in Canada carried out a small-scale clinical trial of the drug in five patients with advanced brain tumours.

Over the past year or two there have been several articles in the news and on the internet about DCA, which was claimed to be cheap, safe and “kill most cancers”.

Understandably this  caused a great deal of interest, especially as DCA is an off-patent drug and appears to be non-toxic to humans (although it can cause significant side effects, as we’ll see later).

But before we jump to conclusions and hail DCA as a ‘wonder drug’, we need to look at the science behind the headlines.

What is DCA and how does it work?

All our cells need energy to grow and function, including cancer cells. Simply put, our cells usually generate energy by breaking down sugar (glucose). To do this, they use a process known as the Krebs cycle, which takes place in tiny structures within the cell called mitochondria (the ‘power stations’ of the cell).

But cancer cells bypass this cycle and produce energy using a simpler process, known as glycolysis, which takes place outside the mitochondria in the cell’s cytoplasm (the main part of the cell). This was first noticed by Nobel prize-winning German scientist Otto Warburg back in the 1920s.

A mitochondrion

Mitochondria are the ‘power stations’ in our cells

Mitochondria play a crucial role in cells. As well as generating energy for the cell, they can also trigger the cell to die if it is faulty – a process that helps stop cancers from forming in the first place.

Because cancer cells seem to switch off their mitochondria, scientists think this is one way in which cancer cells are able to evade death and remain immortal.

DCA, or dichloroacetate, is a very simple chemical and is similar to some of the chemicals involved in the Krebs cycle. In 2007,  researchers at the University of Alberta (led by Evangelos Michelakis) found that adding DCA to cancer cells grown in the lab kick-starts the Krebs cycle, turning the mitochondria back on again. This caused the cancer cells to stop multiplying and die. The team discovered that DCA didn’t affect healthy cells, because their mitochondria were functioning normally.

DCA has been tested as a treatment for children and adults with certain rare metabolic disorders.  This means that, at the doses needed to treat these diseases at least, DCA has been through clinical trials aimed at assessing its safety. Based on their results, the researchers have proposed that DCA could also be useful in treating cancer.

To begin to investigate if this is indeed the case, Michelakis and his team started by carrying out experiments on cancer cells grown in the lab. The team also studied rats that had been injected with cancer cells. They found that DCA could slow the growth of the rats’ tumours, and reduce their size. This did not prove that the cancers were completely cured, or that DCA could prevent cancers from growing.

It is important to stress that DCA had not then been tested as a cancer treatment in humans, despite the implication in news headlines that it “kills most cancers”. There are many research papers produced by scientists around the world every year that reveal potential new treatments for cancer. But it is important that every discovery is carefully investigated to make sure that it is effective and safe for use in patients, and DCA is no exception.

The University of Alberta researchers received approval for a human cancer trial in September 2007, involving 50 patients.  Now they have published the first results from five of those patients in the journal Science Translational Medicine.

The new trial

In this study, Michelakis and his team gave DCA to five patients with advanced glioblastoma, a type of brain tumour, in combination with surgery, radiotherapy and a drug called temozolomide.  It’s important to point out that the aim of this study was not to find out whether DCA could treat glioblastoma, but to figure out the safest dose to use for cancer patients. We already know that the drug can be safely given to humans – although it can cause side effects – but this is the first time it has been tested in people with cancer.

The study shed light on the dose that could be given to patients without causing nerve problems or other serious side effects.  Four patients were still alive after 18 months, and three showed some shrinkage of their tumour, but it is impossible to tell with such a small study whether this is longer than might be expected. And, given that they were also receiving other treatment, it’s hard to know if it was due to DCA at all.

As well as this small trial, the researchers also looked at the effect of DCA on tumour samples from 49 other glioblastoma patients.  They found that DCA could switch mitochondria back on in the cancer cells, although – crucially – it’s still not clear exactly how it’s doing this.

Finally, the team looked at tumour samples taken from the five patients on the trial, both before and after treatment with DCA, and found that the drug was again helping to switch mitochondria on. They also discovered other differences in the cancer cells’ metabolism before and after treatment.

A key gap in this trial is that, as we’ve mentioned above,  it’s not clear exactly how DCA is working. The researchers suggest that the drug may target cancer stem cells and prevent the growth of blood vessels into tumour, although they didn’t actually prove this.

Is it safe?

These results show that lower doses of DCA could, at least in theory, be given to cancer patients while avoiding some of the damaging side effects seen at higher doses. For example, a clinical trial of DCA for a childhood disease found that the drug caused significant side effects, affecting the nervous system. It is also known to be an environmental pollutant. And researchers have found that DCA can actually cause cancer in animals.

This is not necessarily a barrier to the use of DCA as a treatment for cancer – there are a number of powerful cancer drugs that are carcinogens themselves. And this is why we need to test them in clinical trials (as Michelakis and his team have begun to do here) to discover how they can be safely used to treat patients while minimising any harmful effects.

Why can’t we use it now?

It is understandable that people with cancer will want to try everything possible to help treat their disease. However, there is still no evidence – yet – to support the immediate use of DCA to treat cancer patients.

The trial in Canada is being conducted under stringent conditions both to ensure the validity of the results and to protect the participants from any unforeseen effects. Further clinical trials of DCA using more patients will help determine whether the treatment is more effective than the cancer therapies that are currently available.

There are reports that people are buying personal supplies of DCA from sources such as the internet. Cancer Research UK would strongly advise against this, as DCA still has not been shown to actually treat tumours successfully in patients. And it may be harmful when given to cancer patients without accurate dosing and medical supervision.

What will happen in the future?

It is clear that DCA is an intriguing drug – one of many currently being investigated by scientists around the world. It will be interesting to see the results of more extensive lab-based experiments and larger clinical trials of DCA. And cancer cell metabolism is certainly a productive area of research that we’re actively funding.

The fact that DCA is off-patent is no barrier to its development as a treatment for cancer. For example, Cancer Research UK has secured a licence for an off-patent drug called fenretinide, which could be used to treat rare childhood cancers. And there is certainly no “conspiracy” by pharmaceutical companies to prevent research into DCA – there is just not enough evidence at the moment to support its widespread use to treat patients.

While these results are intriguing, it is unlikely that this one compound represents “the cure” for cancer – and it is also unlikely that DCA is the “wonder drug” that the headlines portray. Cancer is a complex and multi-faceted disease, and it can be caused by a range of different faults within the cell. It is unlikely that any single drug could ever treat all forms of the disease.

There are many promising new treatments for cancer currently in development, funded by organisations across the globe – including Cancer Research UK.   If anything, these new results show why research is so important in bringing safe and effective treatments to people with cancer – they don’t provide definitive answers, but they support further investigations which may yield benefits for patients in the future.

Kat


Further reading:


Updates

16th May 2011: Several websites are reporting that last week ‘cancer was cured without anyone reporting on it’. This is not true and seems, we think, to have arisen from a misreading of the date on the most recent paper on DCA (which was published on May 12th 2010 – i.e. this time last year).

Everything we wrote in the post and comments below stands – DCA is still only a ‘potential’ cancer treatment, and more research is needed to find out whether it’s safer or more effective than existing therapies.

Henry

17th January 2012: A number of scientific papers investigating DCA have been published over the past year or so by researchers around the world – we thought we would highlight some of them here for people who are interested in the current state of DCA research. However, it’s important to remember that most of these studies have only been done using cancer cells grown in the lab, and we still don’t have solid evidence from clinical trials that DCA is effective at treating cancer in patients.

It’s clear from these papers – and others that we don’t have room to highlight – that DCA and cancer metabolism is an active and exciting research area at the moment. Right now, Cancer Research UK isn’t directly funding research specifically into DCA, but we are funding projects investigating various aspects of cancer metabolism, which may touch on it.

As we’ve previously explained, we give out funding in response to applications from researchers, and only fund the very best science that will benefit cancer patients. So if a researcher applied to us for funding to study DCA, their application would be judged on its scientific merits like all the rest.

Kat


Key references:

  • P. Kaufmann, et al (2006). Dichloroacetate causes toxic neuropathy in MELAS Neurology, 66, 324-330
  • Michelakis ED, et al (2010). Metabolic modulation of glioblastoma with dichloroacetate. Science translational medicine, 2 (31) PMID: 20463368
  • S Bonnet et al, (2007). A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth Cancer Cell, 11 (1), 37-51 DOI: 10.1016/j.ccr.2006.10.020

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Comments

Sophia February 23, 2012

I would like to add that medicor cancer centres in Canada are actually treating people with DCA, in combination with tetrathiomolybdate. The last is a drug that I would not consider administering without medical supervision. They even have a few case studies, but this was not updated since 2009 as far as I could see (a pity). The case studies note the exact treatment as well as side effects (mostly neuropathy, which is also a possible side effect of chemo).
http://www.medicorcancer.com/dca-reports.html
Apparently you can be treated by these centres, even in other countries, cost is about 2000€ for the first four weeks of treatment (rough calculation, do not know in pounds). Some would say that this is another money making thing, but even if they only help 5 people out of a 100, that is better than 0.
Just a note: my husband has small cell lung cancer, standard therapies give him another six months at the most. We were unable to find doctors/oncologists willing to help him with alternative treatment (he is from Italy), the standard answer is: we do not know this drug. But they are willing to treat him with expensive standard therapies, allthough they know that it will not work. We will buy over the internet, allthough we are not sure whether it is a reliable source. And that is the problem: because you are not being helped over the “normal” channels, you end up doing things that you know might be stupid.
Another note: a clinical trial on DCA finished in December 2011, but the results will only be published end of 2012. My husband cannot wait until the end of this year. People with cancer do not have time.

Tom February 3, 2012

Well, Kat, I guess you’re just doing your job answering these posts, but your “Because these trials are already under way, it would not be a good use of our supporters’ money to replicate work being done elsewhere” is not going to wash — of course it’s not. Nobody is asking Cancer Research UK to replicate anyone’s work. As you know and everyone knows, research is a field that contributes very valuably to the field of knowledge in pretty much direct proportion to the number of people, and talentedness of those people, and the equipment available to those people — in other words, the amount of capital — that goes into it. It’s silly to argue that point.

As for this:
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— well, how ridiculous. It washes even less.

Kat Arney February 3, 2012

Hi Tom,
At the moment, early stage trials of DCA are currently being carried out in the US and Canada http://clinicaltrials.gov/ct2/results?term=dichloroacetate+cancer and we look forward to seeing the full results. Because these trials are already under way, it would not be a good use of our supporters’ money to replicate work being done elsewhere.

Furthermore, we recently spotted this report that the US company Viral Genetics has been granted a patent for the use of DCA to treat cancer: http://www.businesswire.com/news/home/20111121006368/en/Patent-Licensed-Exclusively-Viral-Genetics-Granted-DCA We are currently investigating what this means in practice.

Research into DCA – as well as many other aspects of tumour metabolism – is ongoing around the world. You may be interested in this recent scientific review from the journal Nature Biotechnology, which talks about several promising approaches in this area, including a detailed discussion of DCA: http://www.nature.com/nbt/journal/v28/n9/full/nbt0910-888.html

Kat
Science Information Manager

Tom February 3, 2012

Does all this mean that Cancer Research UK is *not* going to put substantial resources into funding, specifically, trials of DCA? If not, can you explain why not, and assure us that DCA is not going to have the same fate as the anti-cancer drug that was being developed from Vitamin B17 Laetrile, and the work of Raymond Rife (lab smashed up by the FDA, and his notes confisacted, and him dying in mysterious circumstances)?

Mike October 6, 2011

I’m from nigeria and there is a monastry where the monks do alot of research and have so many herbal drugs for a wide range of diseases including cancer, and they Are surprised why the western world has failed to admitt that there is a cure.

tony July 8, 2011

Why do clinical trials? no money can be made on this drug, so $100 million down the toilet.
No major Pharma. will touch it.

Carine Hartman June 1, 2011

I spoke to Prof. Michelakis this week and just finished doing a story about DCA.The team from the University of Alberta are in Phase 2 with their trials testing it now on more brain cancer sufferers as well as lung and breast cancer patients.
So they tested it on only 49 patients since 2008 – and ALL 49 were healed. And the five terminally ill ones who had at best a year from the worst cancer a human can get? The tumors either shrunk or stopped growing within three months.
I’m sorry. That for me spells a cure: plain and simple. And obviously inexpensive…
Forgive me for being cynical, but money does talk

Tony June 1, 2011

No big bucks to be made = no incentive for either drug companies or researchers = no cure!

Peter May 30, 2011

A good article to read is Cancer as a Metabolic Disease by Prof T Seyfried whose speciality is brain cancer and epilepsy.

Follow on with a web search and the result is interesting for all cancers.

This is therapy you can do yourself and won’t rely on DCA.

Fever / Coley vaccine, if we could get it in the UK would be the cherry on the cake.