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May 14, 2010
DCA And Cancer: More Results
In early 2007 there was quite a stir caused by reports of dichloroacetate (DCA) salts as possible cancer therapies. I didn't cover it as well as I should have here, partly because I was in the final stages of getting laid off from my previous job at the time, but here's a good roundup from Orac while the story was going on. It appeared that dichloroacetate was quite active in a number of cancer cell lines, where it worked by some sort of metabolic disruption pathway, quite possibly involving the Warburg effect through inhibition of mitochondrial PDHK. In short form, what that means is that some of these tumors stop using glucose exclusively as an energy source, and divert more of it into other pathways where it's used as a feedstock for the synthesis of other biomolecules. That allows the cells to get by on less oxygen (since the traditional glucose pathways use up a fair amount), which is particularly important in a solid tumor. This is also tied with with a resistance to apoptosis (programmed cell death), so it makes a pretty good package, if you're a tumor cell. But it does leave them metabolically vulnerable, and there have been attempts over the years to target this. (The latest idea in the area is a kinase called PKM2, a good candidate for the key switch that turns on the whole Warburg effect).
The news sent a lot of people searching for their own sources of dichloroacetic acid, and also was the occasion for a lot of "Unpatentable Cancer Wonder Drug Ignored By Big Pharma" commentary, which is always enjoyable. A new paper is now out in Science Translational Medicine looking at DCA in glioblastoma. That's a good place to look, because aggressive solid tumors of that sort are probably the most vulnerable to a Warburg-effect strategy. The authors found that mitochondia from glioblastoma tissue isolated from a number of patients do indeed show the signs of altered metabolism, which DCA reversed in cell culture. And they present the results of treating 5 patients over a period of months with oral DCA therapy.
How'd it work? They were able to compare pre- and post-therapy tissue samples in only three of the patients, but all three showed signs that more cells were undergoing apoptosis, slowing the growth of the tumors. So this wasn't an amazing cancer-disappears result, but it definitely keeps the story going. Three patients is not enough to draw robust conclusions from, of course, and they did see some (reversible) neuropathy as a side effect, but I'd say that DCA is still worth looking into on a larger scale.
Should cancer patients just up and take it themselves? It's really hard to recommend that, since we still don't know a lot about what's going on with the stuff. But it's also hard to tell someone with a refractory solid tumor not to try whatever they can get their hands on.
Update: more from Orac, including details of all five patients treated in this study.
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