Mar 28 2012
We frequently deal with fraud and quackery on this blog, because part of our mission is to inform the public about such things, and also they are great examples for explaining the difference between legitimate and dubious medical claims. It is always our goal not just to give a pronouncement about this or that therapy, but to work through the logic and evidence so that or readers will learn how to analyze claims for themselves, or at least know when to be skeptical.
One skepticism-inducing red flag is any treatment that claims to treat a wide range of ailments, especially if those ailments are known to have difference causes and pathophysiologies. Even claiming that one treatment might be effective against all cancer is dubious, because cancer is not one disease, but a category of disease. We are fond of pointing out that there are many types and stages of cancer, and each one requires individualized treatments. As an aside, it is ironic that CAM proponents often simultaneously tout how individualized their treatment approach is, but then claim that one product or treatment can cure all cancer. Meanwhile they criticize the alleged cookie-cutter approach of mainstream medicine, which is actually producing a more and more individualized (and evidence-based) approach to such things as cancer.
In any case – my immediate response to any article or website claiming to treat most or all cancer is to be highly skeptical, but I reserve final judgment until after I read through the details. What kinds of evidence are being presented to support the claims, and what are the alleged mechanisms of action? Are those making the claims being cautious like a scientist should, or are they being promotional like a used-car salesman?
A recent study claiming a potential treatment for many types of cancer has been making the rounds. The title of the article being circulated is, One Drug to Shrink All Tumors. What made me take immediate interest in this article was that it was not on a dubious website, sensational tabloid, or even mainstream news outlet, but on the news section of the American Academy for the Advancement of Science (AAAS) website. This is a report of serious medical research. The title, I suspect, is perhaps a bit more sensational than it otherwise would have been because of a geeky nod to the “one ring to bind them all” Lord of the Rings quote. Regardless of the source and the headline – what is the science here?
What scientists have discovered over the last decade is that some blood cancer cells (leukemia and lymphoma) express on their surface a protein called CD47. This protein acts as a signal to the immune system and prevents it from attacking the cancer cells. The same CD47 protein is expressed on normal blood cells and keeps them safe from the immune system as they circulate around the body. It makes sense that those neoplastic cells that by chance express CD47 are the ones that will survive and develop into a cancer. Those that do not express the protein are probably weeded out by the immune system. Cancer cells are therefore the Darwinian survivors, although not beneficial for the host.
The AAAS is now reporting on a new finding of Dr. Irving Weissman, who made the original CD47 discovery:
“What we’ve shown is that CD47 isn’t just important on leukemias and lymphomas,” says Weissman. “It’s on every single human primary tumor that we tested.” Moreover, Weissman’s lab found that cancer cells always had higher levels of CD47 than did healthy cells. How much CD47 a tumor made could predict the survival odds of a patient.
Not exactly all tumors, but every one tested so far. Still, this is an amazing discovery. It seems that expression of CD47 is a universal or near universal property of all cancer cells, perhaps required for their ability to evade the immune system long enough to become clinically detectable. Weissman and his team then took the next logical step, they created anti-CD47 antibodies and then tested their activity against tumors. They transplanted “human breast, ovary, colon, bladder, brain, liver, and prostate tumors” into mice, and then compared untreated mice to those treated with anti-CD47 antibodies. What they found is that those mice that were treated generally experienced shrinkage of their tumor and a marked decrease in the risk of the tumor spreading. This is not the same thing as a cure, but any treatment that shrinks tumor and prevents metastasis is a useful treatment against cancer and is likely to prolong survival, decrease recurrence, and increase the probability of a cure.
Our experience with past treatments that show similar promise is that they turned out not to be outright cures, but those that worked became useful additional treatments that improve outcome in some cancers. If anti-CD47 antibodies pan out as an effective treatment, it is likely that they too will be added to the anti-cancer armamentarium, but will not be cures by themselves.
So far, so good – we have what sounds like a very plausible mechanism, and reasonable animal data. Further, the scientists express the proper degree of caution and skepticism toward their own research. They point out that anti-CD47 antibodies also allow the immune system to attack healthy blood cells, causing anemia. The decrease in blood counts was short-lived in the mice, but obviously this will be something to watch carefully in human trials. The also report:
“The microenvironment of a real tumor is quite a bit more complicated than the microenvironment of a transplanted tumor,” he notes, “and it’s possible that a real tumor has additional immune suppressing effects.”
Another important question, Jacks says, is how CD47 antibodies would complement existing treatments. “In what ways might they work together and in what ways might they be antagonistic?” Using anti-CD47 in addition to chemotherapy, for example, could be counterproductive if the stress from chemotherapy causes normal cells to produce more CD47 than usual.
Exactly – animal models are great preludes to human studies, but they are not the same as human data. Biological systems are complex, and we cannot predict what factors may affect the response of a native human tumor to this treatment based upon evidence from transplanted tumors. Further, there are other factors that may impact the net effect of this treatment in humans with cancer, such as interactions with chemotherapy or other host responses.
Therefore, there is no substitute for controlled human trials. We cannot and should not base claims of efficacy, or even safety, on a plausible mechanism and encouraging animal data. What we have so far is sufficient justification for phase I clinical trials in humans, and nothing more.
This is a point worth emphasizing, as it is very common for dubious treatments and products to base clinical claims on preliminary basic science or animal data, often backed up by nothing but anecdotes. Together this kind of evidence can make a compelling story to the non-scientist, and that’s what the marketers are counting on. It is helpful to see how real scientists approach the evidence, and the process that is necessary before we can know that a treatment is safe and effective.
Anti-CD47 antibodies are definitely a promising discovery and a treatment to watch. I hope the research pans out and we can add this to our available treatments for cancer. It is possible, even probable, that (if the treatment proves safe and effective) in the future we may test cancers for the presence of CD47, and then then give the treatment only to those who express this protein – further individualizing cancer treatment. Human studies are likely to take 5-10 years, however, and that’s if everything goes well.
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