DCA and Vidaza

Home Forums General DCA Discussion DCA and Vidaza

This topic contains 10 replies, has 7 voices, and was last updated by  Anonymous 5 years, 6 months ago.

Viewing 11 posts - 1 through 11 (of 11 total)
  • Author
  • #3325


    There is a new theory on why DCA stops working after awhile. If true it would be possible to keep DCA working to kill cancer where it does now and make it work in other cancers. 

    A Dr. Ganapathy from the Georgia Medical Center has a paper out in which he explores why it takes a large dose of DCA to incur an anti cancer affect and why such a dose has to be taken over at least three months. I believe this was the same position taken by Dr. Evangelos Michelakis of the University of Alberta. 

    I called Dr. Ganapathy because my experience with DCA was the exact opposite of his thinking. I had a major reduction in Metastatic Colon Cancer tumor size in the first three months. 

    His theory is that a gene, SLC5A8, is not working in most cancer cells. SLC5A8 is a very efficient sodium transporter into all cells. It transports Sodium Dichloroacetate, DCA, into all cells where it is functioning. 

    In researching SLC5A8 and Colon Cancer cells I found that in 48% of colon cancer cells the SLC5A8 gene is NOT turned off. This might explain why DCA was able to kill off as much as 70% of my MCC tumor before it stopped. Even after DCA stopped shrinking my tumor it maintained the tumor in a stable condition for 14 months. 

    Why? Dr. Ganapathy says that DCA can still get into cancer cells where the SLC5A8 gene is not working but it has a much harder time doing so. 

    That would suggest that during the entire 18 months I took DCA it was able to easily kill off any cancer cell where the SLC5A8 gene was working. After DCA killed off all or most of the cells with a functioning SLC5A8 gene it was left with ONLY those cells where the SLC5A8 gene was NOT functioning and was only able to maintain a stable situation. Only kill cells at a rate that they were being replaced. 

    If so Dr. Ganapathy says that there is a fix for the SLC5A8 gene. A DNA Methylation Inhibitor like Vidaza could turn back on the SLC5A8 gene and allow the transport of DCA easily into the remaining cancer cells. If it could do so this could be a cure. 

    Dr. Ganapathy also says that if this is true you could take DCA at a much lower dose, say 25% of what people like me currently use, have used. If so the problem of Peripheral Neuropathy would be substantially reduced if not eliminated. PN has been the reason I and many had to stop using DCA. 

    Also Vidaza is a chemo itself but in this instance would not be used as such and could be used at only 1/3rd of the dose it is currently used at as a chemo. 

    The neat thing to me is that both DCA and Vidaza would be used not to directly kill cancer cells but to cure cancer cells, to correct functions of cancer cells so that they are more normal and can then kill themselves. This suggest to me at least that the cancer cell would not be able to or induced to try to find a way around this therapy like so many cancers do with current chemotherapies. 

    Anyway others are interested in this theory and a Phase II trial may be in the works. 

    I have found a doctor who is willing to work with me off label to try DCA with Vidaza though I will not be doing so immediately. At the moment I am on Folfiri and Avastin which are working very well to at least reduce my tumor load as they say. 

    But I plan on then going with DCA and Vidaza to deliver what I think could be a knock out punch for my MCC and many other cancers.

    It has been almost five years since my initial Colon Cancer diagnosis and I credit being here to DCA. It may now be that DCA will get credit for my being here a while longer.



    A Google shows that Green/Black tea, Butyrate, and SAMe may be DNA Methylation Inhibitors.  Is there anyone who can confirm this?




    If I understand this


    article correct caffeic acid and chlorogenic acid are DNA Methylation Inhibitors. Caffeic acid and chlorogenic can be found in coffe extracts and olive leaf extracts. Anyone who have any insight into this? What effect could one expect compared to Vidaza with respect to the DNA Methylation Inhibitor effect?



    If getting dca into the cancer cells might pose a problem, how about mixing dmso with dca and applying it transdermally? It seems a great solution to me.

    DMSO on its own is a powerful substance and has been shown to convert some cancer cells to normal, especially if combined with msm.

    Check it out here:



    By doing so one may not need to use a lot of dca to achieve good results sins the dmso has an affinity to cancer cells and grabs the dca strait into the cancer cells, this would probably also avoid some of the neuropathy problems if not completely.     




    Vidaza's demethylating action not only 'corrects' cells behavior, but also acts as a potent inhibitor of retroviruses in two distinct ways (both in transcription and reverse transcription of retroviruses). I mention this because the retrovirus HTLV has been cultured from some GI cancers, so I'd recommend that patients take a blood test for HTLV in order to know if it's part of their illness. In the case of HTLV infection and cancerous / precancerous situations (e.g. MDS), Vidaza's demethylating effect helps both as cellular reformer (if you will), and antiretroviral agent. A recent article regarding a patient in Greece showed that 8 months of Vidaza not only eradicating HTLV from the patient, but normalized all of the patient's blood counts. Also worth mentioning is that Vidaza affects both DNA & RNA, whereas other demethlylating agents only affect DNA.



    Last May 2012 Michelakis' study ("Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer" ,  http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2012198a.html ) mentions DCA-Vidaza increased therapeutic efficacy: "Another mechanism of potential resistance maybe the recently reported decrease of the DCA transporter SLC5A8, via methylation, is cancer tissues.75 Babu et al. reversed this by increasing the expression of SLC5A8 with the DNA

    methylation inhibitor 50-Azadc, potentiating the anticancer effects of DCA."

    In fact the referred Babu et al. document ("Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate" , http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140604/?tool=pubmed ) reports: "The findings that dichloroacetate induces cell death selectively in tumor cells at low concentrations but only if SLC5A8 is expressed have clinical and therapeutic significance. The ability of dichloroacetate to activate PDC via inhibition of PDK in cancer cells provides a mechanistically rational basis for the antitumor activity of the compound. But cancer cells are resistant to the drug because of the absence of an effective transporter for the drug, necessitating requirement of high concentrations of the compound to induce cell death, which unfortunately causes detrimental side effects such as neuropathy. We have demonstrated in the present study that SLC5A8 serves as an active transporter for dichloroacetate. However, since the expression of the transporter is silenced in tumor cells, how can the present findings be relevant to the potential therapeutic use of the drug? The silencing of SLC5A8 in cancer cells occurs via epigenetic mechanisms involving DNA methylation; treatment of cancer cells with 5′-azacytidine, an inhibitor of DNA methylation, re-activates the expression of the gene (Li et al., 2003; Ueno et al., 2004; Hong et al., 2005; Porra et al., 2005; Thangaraju et al., 2006; Park et al., 2007, 2008). DNA methylation plays a critical role in silencing tumor suppressor genes in a variety of cancers, and DNA methylation inhibitors hold promise as anticancer drugs (Baylin, 2005). Two compounds with DNA methylation inhibition activity are in clinical use for treatment of hematologic malignancies. These are 5′-aza-2′-deoxycytidine, also known as decitabine (trade name, Dacogen) and 5′-azacytidine (trade name, Vidaza). In vitro studies have shown that treatment of a variety of cancer cell lines with these compounds re-activates the expression of SLC5A8. We speculate that the same phenomenon would also occur in vivo. Therefore, a combination of a DNA methylation inhibitor and dichloroacetate is likely to be effective for treatment of cancer because the DNA methylation inhibitor would induce the expression of SLC5A8 in tumors, which would then effectively transport dichloroacetate into tumor cells to elicit its antitumor activity. This mode of treatment would reduce considerably the concentration of dichloroacetate necessary for in vivo efficacy as an anticancer agent, thus potentially providing tumor selectivity and also avoiding the detrimental side effects such as neuropathy. The findings of the present study provide a rational basis for such a combination therapy."

    You may find info about also in this robmx's post: http://www.thedcasite.com/dca-forum/topic/new-idea-on-making-dca-work-better-at-lower-doses#post-17





    Some more information regarding DNMT inhibitors:

    (1) The patent (by Celgene, Inc.) for Azacytidine has expired, meaning that anyone can make a generic version of it – why this hasn't happened already puzzles me.

    (2) Clavis Pharma has developed a variant of both Azacytidine and Gemcitabine (called CP-4200 and CP-4126 respectively) that has a lipid attached to the original molecule, which supposedly improves cell permeability, thereby improving the delivery of the medicine to the cells. As with item #1 above, one would expect the price to be lower than the current medication (which can cost $1,000 per dose). See the ClavisPharma site for more details.

    Best wishes.




    may I please ask you to confirm Vidaza patent should be expired: it appears FDA approved just last 2004 (http://en.wikipedia.org/wiki/Azacitidine).




    Doing a search for "Vidaza Patent Expiration" reveals that the RJA site has a PDF file listing many patent expirations, which lists the expiration for Vidaza listed as November 19, 2011. The drug has been around for a VERY long time (more than 40 years), so just because it has been approved in 2004 doesn't mean it hasn't been used (and patented) overseas for much longer.


    Best wishes.



    I believe we need extended and deep clinical trials of DCA to find out its best  therapeutic efficacy. In case DCA-Vidaza_like (DNMT inhibitors) combination work fine since SLC58A gene (DCA transporter to the cells) is activated again, might it happen that other bad genes (e.g., oncogenes) could be also activated again? 

    As another issue, even if I'm not an expert about,  it sounds quite surprising the results of a previously cited study ("Sodium dichloroacetate selectively targets cells with defects in the mitochondrial ETC." , http://www.ncbi.nlm.nih.gov/pubmed/20533281 ): it refers to in vitro and in vivo cell lines research of DCA, not in a whole organism/humans,  but in my opinion that should make even more urgent DCA clinical trials: "In this study, we undertook a retrospective of DCA in vitro activity to verify and extend previously reported mechanistic

    data.19 We conclude that (i) DCA is relatively inactive in vitro and inhibits cell viability with an IC50 similar to that observed with sodium pyruvate and sodium acetate, (ii) the anti-cancer activity is not selective as DCA displays similar activity toward

    normal cells, (iii) growth suppression generally occurs without apoptosis induction, (iv) DCA depolarizes mitochondria of both normal and tumor cells, and (v) the potassium transporter Kv1.5 has less overall involvement. However, DCA showed

    increased activity against cells with mitochondrial defects and effectively synergized with agents known to target mitochondria or interfere with glucose metabolism. These data suggest that clinical evaluation of DCA may benefit from selecting patient

    populations or combination regimes in accordance with the mechanism described here."



    Dan, Tony and others, 

    The answers that everyone is looking for may not have a single  mechanism of action


    responsible for why DCA works, or doesn't.  If cancer cells have adapted to a form of fermentation (aerobic glycolysis aka Warburg effect), is it because respiration (oxidative phosphorylation or OXPHOS) is defective in the cancer cell, or is it because cancer cells via Darwinian selection have learned that glucose oxidation a la <font class=”Apple-style-span” face=”Helvetica”>Warburg protects the cancer cell from death pathways involved when mitochondrial metabolism is active?  If respiration was indeed defective, and DCA restored respiration by inhibiting  PDK (pyruvate dehydrogenase kinase) and forcing the cancer cell to utilize OXPHOS for ATP production, then that  mechanism of action would at least make sense.  But if respiration in the cancer cell is defective then how would DCA somehow "fix" that defect?  Perhaps Babu et al are correct and that it is not the inhibition of PDK by DCA that is the reason for its anti-cancer effect. </font>

    Whatever the effect that DCA has, it appears to do something of benefit AGAINST cancer in some patients, at least anecdotally.  For me, this site is a possible Rosetta stone to assess whether or not this assumption of DCA activity is real or not.  If I were at a large university center, I would focus on pancreatic cancer and use the best treatment available as one arm of the study and DCA as monotherapy in the other arm. If I saw some evidence of DCA anti-cancer activity  e.g., PET scan activity markedly decreased within weeks of DCA initiation, I would then feel justified to adding DCA to other agents of known activity against pancreatic cancer.  I might also do an exploratory study of a DNA methyltransferase inhibitor + DCA involving 10 patients to get a sense of any brilliant anti-CA activity.  

    Right now, at least on this site, we have a pot pourri of stories that are hard to sort out. Was DCA ONLY used?  If so, was the dosing relatively uniform?  Were baseline studies performed and if so, were  follow-up studies while on DCA obtained? 

    I realize that most of you are not in healthcare but the basic premises of good detective work in medicine are logical and rational. There still may be hope that those of you who have some significant documentation of response to DCA will work with docs like me to discern if your records can lead to a reasonable conclusion as to DCA efficacy, or not. 

     Stephen B. Strum, MD, FACP

    Board Certified: Internal Medicine, Medical Oncology

Viewing 11 posts - 1 through 11 (of 11 total)

You must be logged in to reply to this topic.

Comments Off

Comments are closed.