DCA (dichloroacetate) --University of Alberta

UPDATE March 15, 2007
The University of Alberta Discovery

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.

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 tumors.

Michelakis and his colleagues, including post-doctoral fellow Dr. Sebastien Bonnet, have published the results of their research in the journal Cancer Cell.

Scientists and doctors have used DCA for decades to treat children with inborn errors of metabolism due to mitochondrial diseases. Mitochondria, the energy producing units in cells, have been connected with cancer since the 1930s, when researchers first noticed that these organelles dysfunction when cancer is present.

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.

"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. "One of the really exciting things about this compound is that it might be able to treat many different forms of cancer”.

Another encouraging thing about DCA is that, being so small, it is easily absorbed in the body, and, after oral intake, it can reach areas in the body that other drugs cannot, making it possible to treat brain cancers, for example.

Also, because DCA has been used in both healthy people and sick patients with mitochondrial diseases, researchers already know that it is a relatively non-toxic molecule that can be immediately tested patients with cancer.

”The results are intriguing because they point to the critical role that mitochondria play: they impart a unique trait to cancer cells that can be exploited for cancer therapy”
Dario Alteri
Director University of Massachusetts Cancer Center

Investing in Research

The DCA compound is not patented and not owned by any pharmaceutical company, and, therefore, would likely be an inexpensive drug to administer, says Michelakis, the Canada Research Chair in Pulmonary Hypertension and Director of the Pulmonary Hypertension Program with Capital Health, one of Canada’s largest health authorities.

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.

Michelakis’ research is currently funded by the CIHR, the Canada Foundation for Innovation, the Canada Research Chairs program, and the Alberta Heritage Foundation for Medical Research.

"This preliminary research is encouraging and offers hope to thousands of Canadians and all others around the world who are afflicted by cancer, as it accelerates our understanding of and action around targeted cancer treatments," said Dr. Philip Branton, Scientific Director of the CIHR Institute of Cancer.

DCA and Cancer Patients

The University of Alberta’s DCA Research Team is set to launch clinical trials on humans in the spring of 2007 pending government approval. Knowing that thousands of cancer patients die weekly while waiting for a cure, Dr. Michelakis and his team are working at accelerated speed, condensing research that usually takes years into months. Fundraisers at the University of Alberta are determined to raise the money to allow this next phase of research to begin. Once Health Canada grants formal approval, the University of Alberta’s Research Team will begin testing DCA on patients living with cancer. Results with regards to the safety and efficacy of treatment should be known late this year.

“If there were a magic bullet, though, it might be something like dichloroacetate, or DCA…”
Newsweek, January 23, 2007


UPDATE 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.

Letter from Dr. Evangelos Michelakis
October 2008

Dear Friends,

This is a short update on our DCA project at the University of Alberta.

We would like to express our gratitude and appreciation for your support in our fund raising efforts. Through donations on this web page and philanthropic foundations we have been able to expand our basic science efforts as well as initiated and run two clinical trials in Edmonton. In collaboration with the Cross Cancer Institute and the Alberta Cancer Board, we are running clinical trials in patients with solid tumours that have failed standard therapies as well as in patients with malignant brain tumours. The objectives of these trials is to determine the safety of DCA as a novel therapy for cancer. We are trying to determine the optimal dose and to monitor potential adverse effects, such as drug interactions and toxicities. This is necessary to do before embarking on more definitive trials to test the effectiveness of this drug in the treatment of cancer. We have enrolled more than half of our target numbers of patients in these trials and we are gaining invaluable experience. Both the progress and the preliminary results are promising, although the detailed outcomes of these trials will be published in medical journals, after their completion.

We are very encouraged by these early results, and are now preparing to initiate additional clinical trials, in Edmonton and in collaboration with other Universities in around the world.

We are gratified to see that other researchers have begun to share our excitement with DCA. Several recent studies have reported findings similar to ours. These include some work suggesting that DCA has anti-cancer effects in endometrial and prostate cancer (see the references at the end of this letter). However a word of caution, these experiments were not done in patients, but rather in animals and test tubes, and so the applicability of these results to human disease has not been determined. They make however, the need for clinical trials even more pressing. We also reiterate that in the absence of knowledge about the safety and effectiveness of this drug in people it is unwise to be taking this agent unsupervised and outside of a clinical trial.

YouTube video

On behalf of the many people here at the University of Alberta that continue to work on DCA,

Thank you very much!

Recent medical reports on DCA:

Letter from Dr. Evangelos Michelakis
June 01, 2007

Dear Friends,

We continue to be moved by your sustained interest and support of our efforts. We have been working tirelessly over the past several months to bring this research from the laboratory to the level of a clinical trial. This is a very challenging endeavor since it is not supported by the pharmaceutical industry. The process of bringing a drug from animal research to clinical trial takes a few years. However over the past 3 months, we have made significant progress towards achieving our goals. We have received help and input from stakeholders, medical and otherwise, and have received input from our health care partners in Alberta to ensure a clinical trial that can address both efficacy and safety of this potential treatment. We have significantly revised and improved our original protocol for Health Canada’s consideration. We would like to remind you that despite the fact that dichloroacetate has been used in humans for over 20 years the appropriate dose for cancer patients remains unknown. There are several unique features of a cancer patient, from body metabolism to a number of unique drugs that only cancer patients are exposed to, that do not allow extrapolations from other conditions. Therefore, extra caution has to be exercised regarding the strategy to identify an optimal dose.

More importantly, we would like to remind you that this work, at least at its early stages, will not be able to be completed without your ongoing support.

Finally, we are very pleased to see that a number of key findings in scientific literature have surfaced over the past six months and appear to support a proposed theory and the potential effectiveness of dichloroacetate or similar drugs as effective therapies for cancer. Prestigious institutions and journals are now putting our work in context with these new developments and have expressed guarded optimism for these efforts. Such a review was recently published at the prestigious journal “Science” with a title “Metabolic Targeting as an Anti-cancer Strategy; Dawn of a New Era?” A copy of this paper can be found in the media section of our website.

Sincerely yours,

Evangelos D. Michelakis, MD, FACC, FAHA
Associate Professor of Medicine (Cardiology)
Director, Pulmonary Hypertension Program
Canada Research Chair in Pulmonary Hypertension

Journal: Gynecol Oncol. 2008 Jun;109(3):394-402
Title: Dichloroacetate induces apoptosis in endometrial cancer cells.
Authors: Wong JY, Huggins GS, Debidda M, Munshi NC, De Vivo I. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA

Journal : Prostate. 2008 Aug 1;68(11):1223-3
Title: Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation.
Authors: Cao W, Yacoub S, Shiverick KT, Namiki K, Sakai Y, Porvasnik S, Urbanek C, Rosser CJ. Department of Urology, University of Florida, Gainesville, Florida, USA

Journal: Proceedings of the National Academy of Sciences, PNAS 2007 104:9445-9450
Title: Metabolic targeting of hypoxia and HIF1 in solid tumors can enhance cytotoxic chemotherapy
Authors: Rob A. Cairns, Ioanna Papandreou, Patrick D. Sutphin, and Nicholas C. Denko Stanford University, Palo Alto, CA, USA

Letter from Dr. Evangelos Michelakis
March 15, 2007

Dear Friends:

Let me first express my heart felt thanks for all of your support. Our entire team has been overwhelmed with your messages of encouragement and hope. We have also heard many stories of heartbreak and loss which serve to accentuate the sense of urgency to find a viable and more humane treatment for cancer. Your support is helping us to move this important work forward.

The research plan for clinical trials, testing DCA as a cancer treatment in human beings, is complex and requires careful planning. We are aware that each day the research is delayed greatly impacts those of you who are living with cancer and those of you caring for someone with cancer. It’s been a mere six weeks since our initial results have been published and we now await approval of our research plan from Health Canada. The approval process will take a number of weeks and possibly months. We will continue to update the website when there are significant developments.

We are optimistic that we will be able to launch the trials within a matter of months, a process that normally takes several years. We are enjoying the support of the University of Alberta Faculty of Medicine & Dentistry and the Alberta Cancer Board, and help from people like you, makes us confident that we will at least succeed in completing this first trial. By itself, taking a drug from the laboratory all the way to completing a clinical trial, is a tremendously difficult process that is almost never completed without the direct support of pharmaceutical industry.

I want to thank all of you who have made contributions to the research fund. We’ve received generous donations, both small and large, from all over the world - from Canada, the USA, China, Holland, Australia, Greece, India, the Philippines and the UK. These funds, almost $100,000, have already helped us secure some of the supplies that we require. However, for the initial research in humans to start, we need to achieve our fundraising goal of $1.5 million. We need this groundswell of support from our global community to grow to insure our success.

On behalf of myself and the Steering Committee for the DCA study, I want to thank you for your caring support and generosity.

Yours truly,

Dr. Evangelos Michelakis

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DCA Update--Health Canada Approves First DCA Clinical Trial in Cancer.pdf98.89 KB

DCA Effectiveness

Doctors from Medicor Cancer Centres (MCC) have introduced a DCA therapy and have published the observation data for 175 cancer patients. Using dichloroacetate (DCA), they have treated more than a quarter thousand cancer patients.

The data from their analysis is summarized below. While the data was gathered from the first 175 patients, it is, according to the doctors from MCC, very similar to the current results.

The doctors from MCC estimate that the organisms of 60 to 70% of their patients responded positively to DCA - the tumors shrank, the cancer marker reduced, the blood test improved, disease stabilized or there was a symptomatic improvement. In some cases, several of these responses were observed. In 30 to 40% of cases, there was no visible or unarguable improvement. Currently it is not possible to compare the results of these response rates to standardized chemotherapy treatments, because the group of patients treated with DCA is too small.

The doctors from MCC published several case reports on their site, describing in detail treatment of specific patients. They were chosen as a variety of responses to DCA treatment as well as forms of cancer and other therapies used apart from DCA. The doctors from MCC stress that these reports should not be used as a guide for self-medication.

Listed below are the detailed analyses of treatment data for patients treated with DCA in Medicor Cancer Centres (MCC). It is important to note that these data do not come from a clinical trial and may prove not be usable during such trials. It might be also helpful to mention that these data are not current now, over 250 patients have undergone DCA treatment, however the new results are very similar to those listed below.

It is very important to understand that all statements and claims mentioned below are that of the MCC researchers and doctors. They are based on their experience with treating patients with DCA.

DCA (dichloroacetate) has been used over a period of 1 year to treat 180 patients with cancer, who mostly exhausted all other methods of treatment. 52% of the patients were male and 48% were female. The patients were from 2 years to 90 years old, with the largest group of 56% ranging from 50 to 69 years of age. The forms of cancer ranging from lung (40 patients), brain (26), colon (25), breast (15) to pelvis (1), spine (1) and thyroid (1) cancers, to name just a few.

The dosage of DCA given to patients varied from 15mg/kg/day to 75mg/kg/day. The doctors from MCC put the average dosage of DCA at 25mg/kg/day. It should be mentioned that doses above 25/mg/kg/day make it more possible for side effects to appear. The case is different with children patients, however, because during lactic acidosis research, the younger patients could be treated with 50mg/kg/day with very limited side effects. Currently, the patients are treated for one to three weeks with dichloroacetate. DCA is not given to them in the week that follows. The exact number of days varies from patient to patient. None of the patients was denied using safe forms of treatment appropriate for their illness.

Half of the patients (90) has been evaluated. For them, the DCA treatment ranged from 4 to 30 weeks. There were three main reasons, why the other half (90) could not be a subject of evaluation.

52 of 90 unevaluated patients died due to reasons unrelated with DCA. The deceased patients were not evaluated, because the period of time, in which were treated with DCA was too short (i.e. less than 4 weeks).

38 unevaluated patients were treated with DCA for less than 4 weeks. When the data was published, 22 of them were still being treated and the remaining 16 stopped DCA treatment for several reasons - in two cases patients experienced confusion, a side effect of the treatment.

The remaining 90 patients were evaluated. In 54 cases (60%), there was a positive response to DCA. Tumors shrank in 10 cases (11%). Tumor markers were reduced for colon cancer (CEA), ovarian cancer (CA-125) and prostate cancer (PSA) in 5 cases (5,5%). During blood tests 7 patients (31%) showed improvement in hemoglobin, liver enzymes, albumin, or damage to the tissue and cancer activity were reduced. Symptoms have improved in 28 cases (31%) - the severity of pain decreased, patients gained weight, they felt relieved of bowel obstruction, their appetites and energy level improved. It is important to note that it is highly unlikely that placebo effect came into play, because the improvement of the symptoms remained for more than 4 weeks. In 36 cases (40%) cancer did not progress while the patients were treated with DCA. It should be also noted that dichloroacetate proved to be more effective with healthier patients. Nevertheless, DCA very often improves the patients quality of life, regardless of the progression stage of their cancers.

The remaining 36 patients (40%) could not be qualified as having positive response to DCA. In 30% (27 patients) there were symptoms of cancer progression in spite of DCA treatment. The remaining 10% (9 patients) showed no visible change (tumors were unmeasurable, no relevant tumor markers could be observed and blood tests did not bring any answers).

The table below lists the findings of the researchers from MCC in specific cases of lung, brain, colon, breast and ovarian cancers.

The table below lists the findings of the researchers from MCC in specific cases of lung, brain, colon, breast and ovarian cancers.

Type of cancer Number of patients Positive response No visible response No response
Non-small cell carcinomas (Lung Cancer) 19 10 (52%) 3 (16%) 6 (32%)
Gliomas (Brain Cancer) 15 11 (73%) 2 (13%) 2 (13%)
Colon Cancer 11 8 (73%) 0 (0%) 3 (27%)
Breast Cancer(MCC researchers advise to interpret these findings with caution) 15 71% No exact data. No exact data.
Ovarian Cancer(MCC researchers advise to interpret these findings with caution) 8 67% No exact data. No exact data.
Other Cancers 32 Similar percentage of responses. Similar percentage of responses. Similar percentage of responses.

When the data were published, 22 patients continued treatment, while the remaining 68 stopped it for various reasons. 7 of them experienced side effects or resigned for other non-medical reasons, 8 began another treatment, 10 were lost to follow-up, 21 found DCA not effective and 15 died. The MCC doctors noted that dichloroacetate needs time to work and end-stage patients often do not have enough time left. The duration of the treatment is based on several factors, which differ from patient to patient. Some patients may be treated with DCA even for over 6 months.

The reported side effects of DCA treatment included fatigue (19% of the patients), numbness (14%), confusion (12%), tremor (9%), sedation (3%), hallucinations (3%), leg weakness (1%) and heartburn (1%). 50% of the patients did not notice any side effects. The MCC doctors have found out that if patients take supplements, the chance of side effects appearing drops. By now it is unclear whether there are any long-term side effects of DCA treatment. Dichloroacetate (DCA) is not toxic, unlike commonly used chemotherapies. Because of the side effects, however, MCC scientists believe that it should be treated as a serious drug and the treatment should be controlled by a physician.

MCC scientists think DCA should be used to treat patients whose cancers keep progressing in spite of conventional treatment. There is a very high probability that dichloroacetate may be used to treat not only brain, breast and lung cancers, but also many other forms (a variety of cancers showed a 50-75% positive response). The doctors from MCC suggest that any person with cancer, who had exhausted all possible, currently available options of treatment, should contact a doctor to evaluate him or her on the possibility of DCA treatment.

At this time it is hard to predict the likelihood of a patient's response to DCA treatment. It is probable that a chemosensivity test (apart from DNA profiling) may be used as a guide. MCC doctors claim that mixing DCA treatment with chemotherapies is not a proper thing to do. However, it is possible if the chemotherapy seems to be failing or a ChemoFit test is performed first.

There has been a reported case of cancer with DCA resistance. Tumor connected with a breast cancer has shrunk during a several months period, but its size increased afterwards.