There is no miracle cure for cancer

You know the game, Telephone? You line up a bunch of people and the person on one end whispers something to their neighbor, who repeats it to the next person in line, and so on. At the other end, the last player says the secret out loud, and then everybody gets a nice chuckle from how distorted the secret has become as it was passed along the line. I rather like Telephone the game. But, lord, how I hate when it happens in real life.

So, this week on the Internet, there's a story circulating that claims scientists have discovered a foolproof, side-effect free cure for cancer … but They (you know, "THEY") are preventing you from getting access to it. This story is like the end of a game of Telephone. There's some real (and interesting!) science going on, but by the time the story made it to Facebook the reality of a promising chemical compound that could be a good treatment for some types of cancer (maybe, scientists aren't sure yet) had become a first-rate conspiracy theory.

The compound in question is dichloroacetate (or DCA), and it's not really anything new. In fact, research into this compound has been going on long enough—and with enough attention from within the field of people who closely follow basic, laboratory chemical research—that I could almost do this entire debunking using only excerpts from four-year-old posts made by Orac, a surgeon and scientist who blogs about this kind of stuff in a much more specialized way than I do.

Here is something fundamental that you need to remember: Every moment of every day, there is tons of research happening that is centered around chemical compounds that might be useful in some medical application. New compounds are discovered. Existing compounds are tested in new ways. Sometimes, one of these compounds looks particularly interesting to a researcher. They'll publish on it, and their school or institution will put out a press release. Basic chemistry isn't much of a news hook, so these press releases tend to speculate about what the compound could be used for, how it might benefit us someday.

There are so many of these sort of press releases floating around at any given time that journalists who focus on medical science talk about them as a separate category. But, just because a compound is interesting in a chemistry sense, or just because it has shown promise in some in vitro laboratory tests, doesn't mean that it will ever be useful in a practical application. It is very common for a compound to kill cancer in a test tube, but not actually do anything in a human body. Sometimes, a compound successfully fights cancer, but isn't actually safe for humans. And, most importantly, "cancer" isn't really one disease. Different cancers have different causes and require different kinds of treatment—even the same cancer at different stages might not be able to be treated the same. A compound could be effective against stage 2 leukemia, but not do a damn thing to treat stage 4 breast cancer.

DCA is just one of those chemical compounds that scientists are excited about. It's made it past some of the most basic, early studies, but we don't yet know how effective it truly is, and what it's effective against. From what I have read about it, the vast majority of research has been in vitro and in animals. Here's Orac on what we know about why, in those settings, it has been an effective treatment against some cancers:

… to boil it down even further, DCA shifts the cell's metabolism from anaerobic to aerobic metabolism. Why, then, would such an activity be useful as an anticancer therapy?

It all boils down to something known as the Warburg effect, which Otto Warburg first described way back in 1928 and reported in Science back in 1956. Over the last five years or so, cancer researchers have been increasingly coming to appreciate the role of abnormalities in metabolism, in particular the mitochondria, in cancer. To put it briefly, many cancers (approximately 60-90%) favor glycolysis, even in the presence of adequate oxygen for oxidative phosphorylation, leading to a voracious appetite for glucose. Indeed, it is this very avidity of cancer cells for glucose that is the basis of the PET scan, which detects the high uptake of a radiolabeled form of glucose by cancer cells relative to the surrounding normal cells.

Over the last few years, there has been a sort of "chicken or the egg" argument about what is more important and what is the first abnormality leading to cancer. The traditional view has long been that mutations in DNA lead to the activation of protooncogenes into cancer-initiating and causing oncogenes and to the shutdown of tumor suppressor genes. Under this model, mutations leading to cancer also lead to the observations of abnormalities in metabolism. In the wake of the DCA furor, there have been data reported suggesting that the metabolic derangements may actually occur first or simultaneously with the mutations.

This fascinating basic science met the public in January 2007, when Michelakis and his colleagues at the University of Alberta in Edmonton published a seminal paper in Cancer Cell. In the study, DCA was tested in multiple cell culture and rodent models of cancer. In rats, tumor weights in animals treated with DCA were approximately 60% lower than the tumors in the untreated control groups. The drug increased apoptosis, decreased proliferation, and inhibits tumor growth by acting on a critical enzyme that controls the switch between aerobic and anaerobic metabolism without harming non-cancerous cells. Even better, DCA had already been FDA-approved for mitochondrial disorders, meaning that using it in humans would be an "off-label" use of an already existing drug to test it in humans. Thus, the regulatory requirements were considerably easier to meet for early drug trials in cancer.

This new round of excitement on the Internet has bubbled up because those same researchers recently published the results of a first, very small clinical trial of DCA. For the first part of the study, the researchers tested DCA on 49 tumors that had been taken out of human patients. They got some good results, and then tested DCA on five actual human cancer patients. But here's the thing—those humans were treated with more than just DCA. In fact, they were also getting chemotherapy and radiation treatments, stuff we already know is effective in some situations against some cancers.

So, why do that? If you're tying to figure out whether DCA is effective, why administer it alongside things we already know are effective? Doesn't that muddle your results?

It would, yes. If efficacy was the thing that was being tested here. Orac again:

For those not familiar with the various types of clinical trials, phase I clinical trials are not trials of efficacy. They are designed to determine two things: dose and dose-limiting side effects. They generally use a few patients (although five patients represent a rather small number, even for a phase I trial, which usually requires around 10 or 20), and it is not uncommon to perform a dose escalation. Researchers don't expect necessarily to see tumor response in a phase I trial, as that is not the purpose of the trial, but it is heartening when tumor shrinkage is observed, for obvious reasons. Phase 0 trials similarly are not therapeutic trials but rather seek to determine if the drug is doing biochemically what it is expected to do based on preclinical studies. The usual design is to take a biopsy of the tumor, test it for biochemical markers in the laboratory, treat the patient with experimental drug, and then resect the tumor. The biochemical markers in the resected tumor are then compared with those measured in the pre-treatment biopsy. The idea is to see whether the drug can recapitulate biochemical changes in actual living tumors in human patients, the idea being that, if it can, then the drug is "hitting the target" (i.e., its molecular target) and therefore "working." Whether its "working" actually shrinks tumors or results in prolonged patient survival is then the next question that has to be tested.

Five different patients, in different stages of cancer, and using different treatment regimens took DCA in addition to their ongoing traditional cancer treatments. One died. When you look at all the patients' tumors, there's evidence that the DCA did what the researchers expected it to do—which is good, and is part of the process of studying a chemical like this—but it isn't the same as evidence that DCA cured anybody.

Basically, as I said before, DCA is an interesting and promising chemical that could, someday end up being a treatment for some cancers. But that has by no means been proven yet. Scientists are studying this chemical the same way they study all promising chemicals. It's a slow process, one that involves many little steps of research—any of which could easily be overblown into something that it is not. This is probably not the last time you will hear about DCA. And there is a good chance that the next time you hear about it, it still won't be because the chemical has been proven to work. You'll just be hearing about another link in the chain of evidence.

The snail's pace of cancer research is frustrating. Especially to people who actually have cancer right now. It's easy to wonder, "Why don't we just give DCA to cancer patients who want to try it, and see what happens?" That's a tough a question. And it doesn't have any easy answer. I'm going to pass this back to Orac just one more time:

… there is always a conflict between wanting to do something now for suffering patients, damn the consequences, and following the scientific method to demonstrate efficacy and safety. Our nation has been at both extremes. Indeed, until 1906, pharmaceutical companies could make essentially any claims and sell essentially anything to the public as a drug without regulation. We all know how well that worked out. Early in the history of the FDA, as Dr Jerome Groopman points out, companies often tested new drugs by sending them to doctors to offer to their patients, asked for little information regarding side effects and complications, and had no standard criteria for efficacy. There was a reason we moved away from such a system.

Many are the lists of new "miracle cures" that have met this same fate. The difference today is that the Internet has allowed news of these drugs to be disseminated to more people than ever before–and faster than every before. Moreover, it has linked patients and activists into mutually supportive disease-specific communities, who can inform and educate each other, as well as publicizing research about their disease and lobbying legislators. The dark side of this power, however, is that it can facilitate the spread of false hope and the demand for a drug after only cell culture and animal work, before it even makes it to human trials.

Emotion is easy. Conspiracy mongering is even easier. Balancing harms versus benefits, risks and rewards, all the while doing the best for each patient that we can is very, very hard.

Here's a couple of links I'd recommend for further reading:

• Dichloroacetate (DCA) and cancer: Déjà vu all over again—This is the recent Orac blog post where the quotes in this post of mine come from. If you're interested, there is a lot more detail in here about DCA, and about the research that's been done on it to date. There are also some good links to previous stuff Orac has written about DCA.


• Another cure for cancer?—This is from the Skeptic blog, where Dr. Steven Novella talks a lot more about the conspiracy theory part of this DCA story, and pokes some neat holes in it.


• The Hidden Cancer Cure—DCA isn't the only supposed perfect cancer killer that is being suppressed by powerful forces. This Steven Novella post, from last February, talks about the standard cancer cure conspiracy narrative, and why it doesn't really mesh with reality. I'd recommend bookmarking this, and pulling it out every time you hear about a miracle cancer cure.