There is the medical equivalent of a tsunami wave building out there, only we don’t know where this one is going to land.
It is called DCA, and we are suddenly receiving requests for information about something few if any of us had heard about as a cancer treatment until this past week.
I suspect some of this rapid explosion is fueled in part by the internet and the rapid exchange of information, and some by advocates who believe in the long-held conspiracy theory that someone is holding back the single simple answer to curing all cancer.
We even received an urgent plea from one media outlet on Thursday asking us to help them out with understanding DCA, since their website was being inundated with internet traffic that was overwhelming their servers.
Before we replace rational discourse with irrational exuberance, it is my personal opinion that a bit of caution is in order. The basic reason for my conservative view is “been there, done that.”
I don’t know the details of how this phenomenon got started, but I can take a stab at an answer.
Do a general internet search on dichloroacetate (the actual name of this material) and cancer doesn’t rise to the top of the list before very recently.
That said, an article appeared in the January 2007 issue of Cancer Cell, written by a researcher at the University of Alberta in Canada.
I do not know the researcher, but the institution is one that is a recognized, established University.
The basic gist of the research report is that cancer cells rely on certain energy pathways that are different from normal cells, similar to the situation that occurs in what we medically call lactic acidosis.
Lactic acidosis in very simple terms occurs in our bodies when we are very ill or may be suddenly severely traumatized. Our cells basically become starved for energy, and switch into other energy pathways that rely less on oxygen, resulting in the production of lactic acid.
As a result, when there are large quantities of lactic acid circulating in our system, it can contribute to a significantly increased risk of death.
What the Alberta researcher hypothesized was that cancer cells also work through similar metabolic pathways. If you could revert them to normal, then the cells would switch back to the typical energy pathway, and either die or convert to normal cells.
Where DCA or dichloroacetic acid fits into this theory is that it can apparently convert the bad metabolic pathways into good ones.
As noted in the conclusions of the study, it can do so while selectively affecting cancer cells and not harming normal cells.
According to the authors of the report, DCA is non-toxic and is currently used in children who have a rare genetic condition where they produce too much lactic acid.
They go on to point out that DCA is used in these children to reverse the condition with minimal or no side effects.
Let me assure you that this is a gross oversimplification of a very complicated discussion. I personally never was a standout in biochemistry, and that was over 35 years ago. Trying to explain this study in plain words is not an easy task.
But the concepts are basic, and the theories of differential cancer cell metabolism have been around for a long time. The paper itself cites something called the Warburg theory espoused in the 1930s as an example of support for this principle.
In fact, for years we have been studying the possibility that improving the microenvironment surrounding cancer cells by increasing oxygen levels of tumors through various means will lead to improved responses to treatments. Hyperbaric oxygen therapy is one example of such previous efforts.
(In contrast, the targeted therapy Avastin is based on the principle that by preventing blood vessel growth in cancers, you will starve the tumors blood supply, oxygen levels will go down and the cancer will slow or stop its growth.)
To demonstrate the concept, the authors in the current report did a number of experiments that came to the conclusion that DCA was in fact effective in meeting the goals of their expectations.
In these experiments in the laboratory, they found that DCA could in fact reverse the abnormal metabolism in several laboratory-based cancer cell lines. DCA also reversed the “immortality” of these test tube cancer cells and induced a process of cell death called apoptosis.
Finally, they injected some of these laboratory-based cancer cell lines into rats who were genetically engineered to have no basic immune system, and found that if they put DCA into their drinking water, the tumor growth was significantly slower than in a comparison group of rats that did not receive DCA.
In one group of rats where DCA was given after the injected tumors had been allowed to grow, the tumors immediately (in the authors’ word) decreased in size.
So far, so good.
But here is where things begin to get a bit dicey.
These are quotes taken directly from the article. The first is from a summary printed at the bottom of the first page of the report:
“The ease of delivery, selectivity, and effectiveness make DCA an attractive candidate for proapoptotic cancer therapy which can be rapidly translated into phase II–III clinical trials.”
In the discussion section of the paper, the authors conclude with the following statement:
Our work identifies the mitochondria-NFAT-Kv channel axis and PDK as critical components of the metabolicelectrical remodeling that characterizes many human
cancers and offers a tantalizing suggestion that DCA may have selective anticancer efficacy in patients. The very recent report of the first randomized long-term clinical trial of oral DCA in children with congenital lactic acidosis (at doses similar to those used in our in vivo experiments) showing that DCA was well tolerated and safe (Stacpoole et al., 2006) suggests a potentially easy translation of our work to clinical oncology.” (Emphasis mine)
In other words, the authors are saying that in their opinion these experiments in the lab and rats suggests that DCA may be a simple, effective treatment for cancer and we should move forward with clinical trials based solely on their theory and their results.
I am not being critical of the authors’ comments, except for describing this as a “potentially easy” process. Nothing in translation from the bench to the bedside is easy.
This is not the first time such suggestive statements have been made. In fact, these types of comments are not unusual in papers of this type.
What I am critical of is the lack of discrimination in judgment of other folks—not the researchers--who have picked up on these lines and rapidly circulated the thought that we have a cure for cancer at hand, and that we must stop doing everything else and get this simple, safe and effective treatment to cancer patients immediately.
Even my own blog was “hit” with such a suggestion this past week.
Well, as they say, if I had a nickel for every time I have heard such a proposition based on this type of evidence, I would be a rich man.
Please try to understand that I am NOT saying this is a theory that won’t work. It may, and if it does prove valuable, that would be terrific.
It is just that I have been around a while and have seen this type of hope and hype just a few times too many.
I have seen cancer patients hopes lifted and dashed so often that I can’t help but be cautious and conservative in my thinking.
Let’s take a look at what we can say.
First, I did a literature search on PubMed looking for articles with the terms dichloroacetic acid and cancer.
Although I didn’t have access to all of the articles, one underlying theme stood out: DCA is an organic chemical that causes liver cancer in laboratory mice when put in their drinking water.
It is NOT non-toxic. It is a byproduct of another chemical called trichloroethylene (TCE), which has been a source of concern as a cancer causing agent for some time. (A simple Google search will give you over 8 million hits on this topic.)
Here is what the Agency for Toxic Substances and Disease Registry has to say about TCE:
“HIGHLIGHTS: Trichloroethylene is a colorless liquid which is used as a solvent for cleaning metal parts. Drinking or breathing high levels of trichloroethylene may cause nervous system effects, liver and lung damage, abnormal heartbeat, coma, and possibly death. Trichloroethylene has been found in at least 852 of the 1,430 National Priorities List sites identified by the Environmental Protection Agency (EPA).”
So before you start going out and adding DCA to your drinking water to prevent cancer, a degree of caution would be very prudent at this point.
Another article that came up in the Google search was a 1983 article from the New England Journal of Medicine.
Here is a quote from that article:
“Despite improvement in their lactic acidemia, all patients but one died of their underlying disease. No serious drug-related toxicity occurred. We conclude that dichloroacetate is a safe and effective adjunct in the treatment of patients with lactic acidosis, although the ultimate prognosis may depend on the underlying disease.”
In other words, the treatment was a success, but the patient died.
But experience is the best teacher in my opinion.
For example, even in the short time this blog has been in “production” I have written articles on other relatively non-toxic substances and their potential role in either preventing or reducing the burden of cancer.
New discoveries about vitamin C and vitamin D come to mind.
We haven’t seen the hue and cry about getting these vitamins into cancer clinical trials, yet based on evidence similar to the DCA paper, there is equal reason to believe that either or both of these vitamins may have a role in cancer prevention and/or cancer treatment.
Still vivid in my mind was something that happened in the early 1970s when I was training to be an oncologist at the National Cancer Institute.
To the best of my recollection, a research report suggested that a particular material was very effective in treating acute leukemia. Once again, mice that had a transplanted leukemia were given this drug, and the leukemia miraculously disappeared.
To demonstrate that this new drug was so non-toxic that the researcher went on to one of the major national morning television shows and injected himself with the drug right there on camera as he touted his new discovery.
The problem was that there were only very, very small amounts of the drug available.
Research centers around the world rapidly picked up the beat, and vied to get their hands on some of this new miracle powder.
Cancer research centers were receiving phone calls with incredible offers of financial support from wealthy patients with leukemia, if they could just get these folks this wonder drug.
The only thing we found out was that it didn’t work at all.
Of course, there are stories on the other side of the aisle so to speak, where simple discoveries in fact have proven to have great benefit in the treatment of some cancers, such as the treatment of promyelocytic leukemia.
But the overwhelming number of promising laboratory experiments have not ended up as effective cancer treatments when they move from the bench to the bedside, if they are even able to get to the bedside in the first place.
It is indeed a long, difficult road that must be traveled to demonstrate that an exciting new idea actually works in the treatment of cancer.
So, pardon me if I am a skeptic. As Jessica Rabbit said, “I am just drawn that way.”
But I am also an optimist, as I have said many times in these pages. I do believe that there are exciting new developments in cancer treatment emerging from laboratories around the world. Maybe DCA is one of them.
Right now, we simply do not know what is going to occur as DCA moves through the research pipeline, first with laboratory confirmation and critical analysis of these findings and then on to the clinic if others review this report and agree that DCA is a promising approach that deserves a clinical trial in the treatment of cancer.
It’s just that I believe in patience, prudence and caution because my experience has taught me that those are the best guidelines to follow in assessing reports such as the one in Cancer Cell.
It is way too soon to know whether this is a cancer treatment breakthrough or an urban legend or something in between.
I am acutely aware that there are cancer patients out there who are fighting every day for their survival, and are hoping that there is one last chance to get a treatment that may prolong or save their lives.
For some of you out there to inappropriately make them feel that DCA is the answer to their prayers based on this single early stage report in a medical research journal is, in my opinion, not acceptable at best and despicable at worst.