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An intriguing part of writing this blog is how much I learn from my patients. It also turns out that I learn ABOUT my patients. I suppose nothing should surprise me about this in the digital age, where presumably all of you can find my address, social security number and probably what brand of oatmeal I like ! (I’ll save you some time there, try McCanns Steel Cut Irish Oatmeal, it’s terrific…). For the past month or so, one after another has come in with the question, “So, what do you think about 4-MU?” or “Did you hear about poliovirus killing cancer?” Actually, I have heard next to nothing about either, but of course I was intrigued as to where my patients get their information.
Starting with the 4-MU story, it seems it was featured on that bastion of “fair and balanced news,” FOX. I sincerely hope that is not the primary source for your news, and that you don’t subscribe exclusively to a certain talk show host who calls everybody but himself the “drive-by media”. If you want serious journalism, I’d suggest the NYT, WSJ, and NPR for a pretty good balance of real news. None of them carried the two stories I’m going to go over here. Further, if you ever hear of a story with interest in medicine, I suggest you go immediately to Google Scholar, which is absolutely wonderful at finding abstracts, patents, and journal articles on almost anything in medicine. And if you want to know if a novel treatment in development is available in your area or anywhere else, for that matter, do your search at ClinicalTrials.gov.
Well, using combinations of all of the above to learn about 4-MU, (which stands for 4-methylumbelliferone) I found that FOX decided to sensationalize a mouse study published by some University of Miami investigators. 4-MU turns out to inhibit synthesis of hyaluronic acid, a major component of synovial fluid and the “goo” or intracellular matrix. It has been studied in the past to inhibit some bacterial and viral replication, and indeed there is even a clinical trial with 4-MU listed as going on in chronic hepatitis. The Miami researchers found that in mouse models 4-MU inhibited prostate cancer metastases, which gained excitement because it is supposedly a non-toxic supplement. While I try to keep an open mind, there is a long history of various natural products working in mouse models that then have little or no activity in the real world of human cancer. We, ourselves, discovered that acai juice and the milk thistle derived molecule, silibinin, had minimal/no activity in prostate cancer, in spite of promising results in animals. My judgment regarding 4-MU is that it would indeed be of interest to study in human prostate cancer, and hopefully it would work, but until such a trial is done, I would not recommend taking it if you find a supplier somewhere on the Internet or similar.
The poliovirus story is a bit more complicated. It gained patient attention via a 60 minutes presentation. Many tumors, including the highly lethal glioblastoma brain tumors, have receptors on their cell surface for the virus. Through very elegant and complex recombinant DNA technology, investigators at Duke University engineered a novel virus that could induce death in the brain tumors after direct injection. In an ongoing Phase I clinical trial, they are seeing dramatic responses after direct injection of the tumors in the brain, in part because of a “violent” immune response. The key here, however, is direct injection. It may be possible to build on this, but direct injection of oncolytic viruses into head and neck cancers, lung cancers, and even prostate cancers in the past have not had the desired results. Moreover, what we really want, is some sort of virus that a) can seek out every metastatic cell in the body [brain tumors seldom metastasize, but kill people by local growth], and b) produce that immune response after infection. I have written elsewhere about the promise of the immune checkpoint inhibitors, and I encourage you to go to my blog site and read about those ongoing efforts. Meanwhile, I hope that the search strategies I have outlined in this blog will help you do your own research to answer the question, “Doc, have you ever heard????….”