I received a question on the discussion forum, in the setting of a lot of internet discussion, about an an agent called dichloroacetate, or DCA, as a potential anticancer therapy.  This excitement is based on a study out of the University of Alberta in Canada, that appeared in the journal Cancer Cell (article here).  This is a very novel molecular therapy approach, and one about which I don’t have a lot of insight yet, but it does provide an opportunity to discuss the gap between a promising result in preclinical studies and a proven anticancer therapy. 

   DCA is an unpatented small molecule that has been used for decades to treat children with rare molecular disorders associated with mitochondrial problems, but it’s not a drug that I have had occasion to use.  Mitochondria are a component of every cell that create energy for the cell, and mitochondrial disorders have been known to be seen with cancer but have been believed to be an effect rather than a key contributing cause of the cancer process.   

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The idea is basically that cancer cells suppress their mitochondria, making the cells resistant to apoptosis, or the normal process of programmed cell death, a sort of self-destruct program built into all cells of the body for certain normal developmental processes but also as a defense mechanism in case the cells mutate too much to work properly.  The work described in the paper demonstrated that multiple types of cancer cells in test tube (in vitro) and animal models could be suppressed and killed after DCA restored the normal ability of mitochondria and led to apoptosis that destroyed cancer cells.  This research suggests it would have no effect on normal non-cancer cells, so it is believed that DCA would not be assocaited with significant side effects. Overall, these results were considered very encouraging for a drug that it inexpensive and orally available.

   And they are.  I would consider them as promising as any pre-clinical work (before human studies).  But they are also very, very early results.  There are thousands of drugs that have been shown to kill cancer cells in vitro, but the vast majority of them fail to prove themselves safe and clinically active enough to be approved by the FDA, with estimates such as only 5 in 5000 actually getting through that process.  It is a time consuming and expensive process, and I’ll describe the challenges further in my next post.  Suffice it to say, however, that it takes 5-15 years for most drugs to go from earliest testing to approved drug. 

   Now, DCA is in a different position, since it’s already an approved and available drug.  In that sense, it’s like studying whether cholesterol lowering-agents like the statins or an arthritis drug like celebrex may fight cancer.  However, the multi-million dollar and time-consuming commitment to develop a drug for a new indication (reason for prescribing it) is generally funded by the company that stands to profit by marketing it.  This means that cheap drugs that are off patent, like DCA or cisplatin, don’t have the same chance of being thoroughly investigated as expensive drugs that can be marketed while protected by a patent for many years (like Alimta, Tarceva, Nexavar, Avastin, and many others). 

   So there are two clear challenges for DCA.  First, although there is a good rationale for it being developed as a molecularly targeted therapy in lung cancer as well as others, it doesn’t have the financial backing of a large pharmaceutical company.  Publicly funded enterprises such as the National Institutes of Health (NIH) can award research grants that provide resources for some basic science (lab-based bench work) and clinical studies (although I would say that, unfortunately, the NIH focuses too much on funding basic science and not enough on cancer work in actual humans).  Canada may not have the financial resources of the US but could also provide some tax-supported funding for this important cancer research from Alberta.  Another means of funding research is the the direct approach, as the lab and lead investigator are seeking contributions to a research fund to support this work.  More information and ways to donate online or via a printed form at the bottom of this page (I’m just offering FYI, not making any appeal here).  The other issue is the time required to test this approach in clinical trials.  Even if the safety of DCA is pretty much established from the work on patients with metabolic disorders, it takes years to test the usefulness of a new drug in phase II and III clinical trials (I’ll go over these concepts more in my next post).  Moreover, the safety of DCA may be very different when combined with chemotherapy or other anticancer therapies, which is one of the ways that the investigators envision DCA being useful in cancer.

    Overall, my opinion based on the single, very early paper about anticancer effects of DCA is that it is as promising as any drug in early testing, but that is a very long ways away from being a proven treatment for cancer in humans.  And while there is a good deal of buzz about it, having the investigator who ran the trial call DCA a breakthough for cancer is kind of like a new parent saying their baby is adorable and destined for great things.  It’s too early to declare any victory, and it’s not the same as someone who isn’t the leader of the project saying that it’s a major step forward.  However, I’ll keep watching, and I’ll definitely be interested if I learn about clinical trials becoming available with DCA in lung cancer.