Subtitles section Play video Print subtitles I have a rather unpleasant secret to tell you. Something that the cancer research community don't really like to talk about. Here it is: "There are no cures for cancer, and it's highly unlikely there ever will be." I'm sorry, that's simply the harsh reality. We may develop better and better treatments, we may develop vaccines or preventative measures, and our lifestyles may improve over time. Our ability to diagnose will steadily improve, and someday the shrink ray or biofilters or nanobots may make cancer a minor inconvenience, but cancer is built into our biology. It's... us, gone abnormal. It is as diverse as we are, and possessed of the same adaptability, resistance to harm, and made of the same stuff. This is what makes it so difficult to treat. Poisoning cancer means poisoning a part of us that's acting selfishly. The differences between our normal cells and our cancer cells are small, and scientists attempt to exploit those small differences to design cancer therapies that are more harmful to the patient's cancer than it is to the cancer patient. So, a lot of people have sent me a request to address the recent announcement by the University of Alberta on the cure for cancer called DCA. The very phrase "cure for cancer" tells me that a researcher is not writing this press release. It's mostly filled with misinformation, or at least marketing spin, and I want to explain the why and how of DCA for cancer. It is a promising drug for cancer therapy, but the evidence doesn't match the hype its receiving. DCA stands for dichloroacetic acid, which is a very small, very simply compound. It's a byproduct of municipal water purification, specifically of chlorination, and getting rid of it safely is the subject of a lot of research. It's not a nice chemical to dump in our waterways, so making sure all of it is recovered is important. DCA has also long been used to treat certain metabolic disorders. It inhibits an enzyme involved in the metabolism of sugar in the mitochondrion. This is important for people who overproduce lactic acid, which DCA helps to reduce the production of. It's been approved for use for lactic acidosis for years, where it's pretty effective. So, we know that DCA is a byproduct of water treatment, and we know that there medical uses of it for metabolic disorders. Now we get to the exciting part. It turns out it has metabolic effects on cancer as well. Cancer cells have long been known to have unusual mitochondrial biology, going back to a German doctor named Warburg, and the effect is called the Warburg effect. Tumor cells often use glycolysis instead of oxygen based respiration. Glycolysis is an alternate way of burning sugar that is less efficient, but not dependent on the delivery of oxygen. This means that a tumor can grow beyond the ability of the blood vessels around it to support its normal oxygen demands. That's why tumors are often dense masses, hard to penetrate with normal chemotherapies. A second effect of glycolysis is that it interferes with the normal cellular suicide that damaged cells commit, called apoptosis or apoPtosis. If we could coax cancer cells into only using respiration, they wouldn't be able to grow so big without more blood vessels to supply oxygen. If we could coax their mitochondrion into normal functioning, it could trigger cellular suicide responses, as they recognize themselves to be malfunctioning. So, does DCA do this? Yes, it does, in certain types of tumor, especially in neuroblastoma, although the results are still pretty preliminary. What makes DCA most valuable, in my estimation, is that it cooperates or synergizes with other types of therapy. It helps the action of traditional chemo, by making the cancer cells more sensitive to oxygen metabolism, or more frail to metabolic interference. So far, it's proven that it increases the effect of radiation, gene therapy and DCA is pretty exciting as an adjunct therapy, and that's currently being examined. By itself, it's effective on a few types of cancers that are very glycolytic but in combination it may improve outcomes for a broader variety of cancers. It's important not to uncork the celebratory bottle of champagne just yet, though. So far the effects are pretty modest and there are some toxic effects that limit the dosage that can be used. When it was tested in cancer cells grown in a flask, it reduces progression in some cases. In the case of some cell lines, it increased the cellular suicide level by 10 fold. However, in others, it actually made the cancer cells "worse" by protecting them from oxygen starvation. It was also shown to interfere in some cases with the front-line drugs cisplatin and doxorubicin. We're going to have to work out these paradoxes before it can go into use. In animal testing, the results were a little more positive. Colon cancer tumors showed 20 to 40 percent reductions in progression vs. untreated animals. That's not as good as some present drugs, but still pretty effective. So, modestly effective in cells, reasonably effective in animals, what about human testing? Human clinical testing has never been conducted in the US. Canada ran a safe dose study, where they give patients escalating doses to determine what amount is safe, and what amount is effective. We know from prior studies that DCA can, ironically, cause cancer, and that it can cause neuropathy, or nerve damage which can be severe at therapeutic doses that someone might get for lactic acidosis. The Canadian dose escalation started in 2007. 50 patients were enrolled, but only 5 were actually treated, and as I understand it they spent 800,000 dollars for that very small result. The official conclusion of the study is linked in the underbar, but the short version is that the investigators said that no conclusions could be drawn about the efficacy and safety of DCA for cancer therapy. So we still have no idea if it will be very effective. Five treated patients, in the history of a drug, is not enough data to go on. DCA is one of many possible avenues that cancer researchers are pursuing, a useful adjunct to conventional therapy, although it's still in the early stages of testing and research. Why is it being promoted? Why am I getting so many messages about it, when no-one has asked me about cancer immunotherapy that is a LOT more exciting and promising? It's because DCA is an unpatentable substance. It's too historical for anyone to claim to have invented it. That means that the drug companies have little or no interest in it. Who can blame them? Oh, I know, Big Evil Pharma love making money, but well... so does every company, and most employees, too, come to that. We run businesses at a profit, and if DCA can't be sold for profit, then how will those companies recoup the cost of the 2 to 500 million dollars it may take to bring the drug to market? The management of the drug companies are tasked with making money. DCA won't likely compete with existing drugs, may enhance effectiveness of those products, but it's not a profitable venture for them to invest hundreds of millions of dollars into. We can deplore the profit motive, but the purpose of business is to make money. Either the government or a non-profit will have to step in to complete the safety review, testing and manufacture. The University of Alberta are funding their DCA research program on a combination of public donations and government funding. I think the reason why this topic keeps hitting the news and email forwards is that they have hired marketing people to get the word out, to promote the product, and to try to get some funds. So, they take the story of a compound with a small but useful effect in certain tumors, and they blow it up to epic proportions, the cure for cancer. I'm thinking it's time for a third C0nc0rdance's Law, so here it is: "Any scientific discovery announced in a press release is almost always less impressive than it sounds." c0nc0rdance's Third Law. I hope I haven't discouraged any of you out there from a future in cancer research. We may never find a cure, but it's one of those jobs where you wake up in the morning with the potential to save thousands of lives. Nothing beats that feeling. Thanks for watching.
B1 cancer therapy oxygen effective metabolic glycolysis DCA and Cancer 23 10 VoiceTube posted on 2016/09/29 More Share Save Report Video vocabulary