Dichloroacetic acid and rapamycin synergistically inhibit tumor progression

Was just reviewing and looking up the various drugs being tested in the ITP these days (see my post on this here: Suggestions for ITP drugs to test - #98 by RapAdmin


Dichloroacetic acid (which is in the 2021 ITP cohort) looks really interesting … I’m going to be going through PubMed and adding studies that seem helpful…

Small molecule offers big hope against cancer


and a new study:

Dichloroacetic acid and rapamycin synergistically inhibit tumor progression

Mammalian target of rapamycin (mTOR) controls cellular anabolism, and mTOR signaling is hyperactive in most cancer cells. As a result, inhibition of mTOR signaling benefits cancer patients. Rapamycin is a US Food and Drug Administration (FDA)-approved drug, a specific mTOR complex 1 (mTORC1) inhibitor, for the treatment of several different types of cancer. However, rapamycin is reported to inhibit cancer growth rather than induce apoptosis. Pyruvate dehydrogenase complex (PDHc) is the gatekeeper for mitochondrial pyruvate oxidation. PDHc inactivation has been observed in a number of cancer cells, and this alteration protects cancer cells from senescence and nicotinamide adenine dinucleotide (NAD+‍) exhaustion. In this paper, we describe our finding that rapamycin treatment promotes pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) phosphorylation and leads to PDHc inactivation dependent on mTOR signaling inhibition in cells. This inactivation reduces the sensitivity of cancer cells’ response to rapamycin. As a result, rebooting PDHc activity with dichloroacetic acid (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, promotes cancer cells’ susceptibility to rapamycin treatment in vitro and in vivo.

Open Access Paper: Dichloroacetic acid and rapamycin synergistically inhibit tumor progression - PMC

A 2019 Review document:

An extensive body of literature describes anticancer property of dichloroacetate (DCA), but its effective clinical administration in cancer therapy is still limited to clinical trials. The occurrence of side effects such as neurotoxicity as well as the suspicion of DCA carcinogenicity still restricts the clinical use of DCA. However, in the last years, the number of reports supporting DCA employment against cancer increased also because of the great interest in targeting metabolism of tumour cells. Dissecting DCA mechanism of action helped to understand the bases of its selective efficacy against cancer cells. A successful coadministration of DCA with conventional chemotherapy, radiotherapy, other drugs, or natural compounds has been tested in several cancer models. New drug delivery systems and multiaction compounds containing DCA and other drugs seem to ameliorate bioavailability and appear more efficient thanks to a synergistic action of multiple agents. The spread of reports supporting the efficiency of DCA in cancer therapy has prompted additional studies that let to find other potential molecular targets of DCA. Interestingly, DCA could significantly affect cancer stem cell fraction and contribute to cancer eradication. Collectively, these findings provide a strong rationale towards novel clinical translational studies of DCA in cancer therapy.


With the number of interventions that work on mice, I fear they will attain immortality before we do.


“The next step is to run clinical trials of DCA in people with cancer. “

That was written 16 yrs ago?

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I’ve found it difficult to source. Amazon seems to sell a product called Sodium Dichloroacetate, but not sure this is the same.

Well, I don’t think big pharma or the health industry in general, i.e. Medicare Advantage plans, that make money from the government for treating you, are going to be interested in a cheap effective cure for cancer. I have no idea how effective DCA is, but you can bet your a*s that no company in America is going to invest big money in a clinical trial. We will have to rely on foreign governments with a different healthcare views for that.


I have not had time to fully review all the research since this initial study popped up in 2007… if someone has the time and interest, perhaps they can.

But - the issue may be the same as with rapamycin; it (DCA) is a generic medication showing potential in a new indication - but there is no financial incentive to do the human clinical studies, so nothing happens.

And, after reading this article, I became less enthusiastic about this compound: Why every claim of an exciting new cancer cure needs close examination - The Globe and Mail


I would lean towards the compound being ineffective rather than the conspiracy theory. People can certainly get NIH funding for non patent drugs.

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Review the following two papers;


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really? I don’t believe its any conspiracy theory, just the Gov’t doesn’t like to fund clinical trials. Certainly not so much for phase 2 or phase 3 human clinical trials it seems. How long have they been trying to get money for TAME / Metformin study - I think its on year 8 or 9 now that Nir Barzelai and gang have been working on it… There does not seem to be much interest in funding a $5 million dollar phase 2, and even less for a $50 million phase 3 trial by any government or non-government agency.


You could be right. I would think funding to cure cancer would be easier than for longevity?

I’ve never heard of a non-Pharma funded human clinical trial. They may be out there but they are very rare. I searched on “example of government funding of human clinical trial generic drugs - Google Search” and could find nothing.


Again, you’re right. I’m s you know more about this than I do,

Thank you, very much appreciated. I will review. :slight_smile:

The whole of the ITP program runs on about 2 million a year. Much less than a Phase 2 RCT.

I’m not sure i’m right… thats just what I’ve seen (or not seen). I’m happy to be shown to be wrong.

But I think the bigger issue is likely that the science hasn’t moved forward much… at least from what I can see from a cursory glance at it.

Unlike with longevity drugs, there is a ton of research being done on Cancer by traditional pharma, so it seems likely that the research on DCA is very minimal compared to the funds being poured into other cancer therapeutics, so I suspect if you have cancer, the traditional pharma/biotech route is probably the best option.

So I’m agreeing more generally with you that the more I look at DCA the more it seems underwhelming, as they point out in this news item: Why every claim of an exciting new cancer cure needs close examination - The Globe and Mail


@rapadmin Thank you for sharing the article, I’d like to offer a rebuttal to the claim of “conspiracy theory.”

The article states that “some conspiracy theorists take it a step further, saying that health organizations and cancer charities are in on the plot to keep this miracle drug out of sight because they have ties to drug firms and want to keep money flowing their way.”
I consider this a straw man argument; I’m sure you can find people out there who adopt this viewpoint, but it distracts from the real issue: there is too little financial incentive for pharma to conduct clinical research into promising compounds that cannot be patented, yet they are the only real players with the regulatory expertise and funding to bring these potential medicines to market under our current regulatory regime.

Quite frankly, our regulatory regime for medicine is one where money (and therefore corporate interests) talks. To bring medicines to market, companies must invest incredible amounts of time, effort and money into R&D as well as clinical trials. It is not a conspiracy theory to say that corporate entities are acting according to their financial incentives, which clearly lie in patentable compounds (especially for chronic/terminal illnesses such as kidney failure/cancer) that can generate financials windfalls to justify the massive investments needed to bring a medicine to market.
That is not a problem in itself, but it is when our regulatory regime leaves these companies as the only entities that can bring medicines to market. While this system has its advantages in weeding out dubious compounds (Aduhelm not included), this system also has very real negative consequences for patients, such as your lawyer friend who had to leave the country to get the cancer treatment he needed.

I think you’ve hinted at one solution to some of the issues with this system, which is that we need a far more robust public funding mechanism for researching and bringing to market promising medicines that cannot be patented. I think the regulatory regime for our medical system in the US is suboptimal, to say it lightly, especially when considering the amounts of money we spend on healthcare relative to our health outcomes as a nation.