Of disulfiram, the publication of our international team’s work in Nature and nonprofit drugs

» CZECH / ČESKY

Boris Cvek, 23.12.17
based upon Boris Cvek’s interview (in Czech) Významný objev v léčbě rakoviny otevírá nové cesty (A significant discovery in cancer treatment opens new ways) in Hlídací pes (Watchdog) 23.12.17 – slightly edited by –vjr-

Disulfiram (antabuse) and state of today’s research

bcupolDuring the last years we confirmed that disulfiram, also known as antabuse, is effective against cancer at cell level and in animals.

Over the past forty years, dozens of articles have been published on this subject. The problem was that most of them explained the effectiveness of disulfiram in not a clear way. In our article Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4 in the Nature journal, we bring a perhaps definitive explanation. We have shown how disulfiram kills cancer at the level of cells and in animals that have tumors.

jiri-bartekMost of the work was done by Jiří Bártek‘s team of his Olomouc laboratory. Also noteworthy is a study, part of our article, by colleagues from Denmark who have shown that among alcoholics with cancer, those who took disulfiram were healthier.

We also confirmed my old hypothesis that one particular compound produced in the body from disulfiram and copper is responsible for its antitumor activity. Previously, I called it CuET. It is highly remarkable that it accumulates in tumors. This is the dream of all oncologists – to get the cure into the tumor and, on the contrary, not to have it in healthy tissues. Hopefully, this will also be confirmed in humans.

In the cells, this substance causes the degradation of proteins to stop. It prevents the removal of waste, more precisely unnecessary proteins, from the tumor cells. They accumulate inside the cell, which then dies. And it prevents it in a unique way, not described previously. This is probably the greatest scientific contribution of our work.

Model of DSF anti-cancer activity in patients
Fig. 4f

Skrott_et_al-2017-Nature_p5-fig4f_cropped

DSF = disulfiram (tetraethylthiuram disulfide)
DTC = diethyldithiocarbamate
CuET = DTC–copper complex (bis (diethyldithiocarbamate)–copper)

The portability of preclinical research on humans

The main problem of all similar preclinical research, i.e. those performed on cells or animals, is their portability to humans. Even if the preclinical results may give hope, it does not necessarily mean that the substance will work in humans. There may be a vast gap between preclinical and clinical research.

Based on our article in Nature, we can not argue that disulfiram will treat cancer in humans. We can only say that clinical trials of disulfiram in oncology patients are needed. And now we give very strong arguments why to begin with them.

Clinical tests
Editor’s note: Phase II clinical trials already started in Olomouc – Phase II Trial of Disulfiram With Copper in Metastatic Breast Cancer (DISC)

If there was a pharmaceutical company that has patented and owns disulfiram, it would begin clinical trials on a wide range of cancerous diseases based on our findings. But disulfiram has no company to care. It has a long history, it can not be patented and therefore not commercially exploited.

If someone would invest money in the clinical trials, and it would turned out that disulfiram actually cures people, someone could start producing it cheaply and selling it cheaply as well. What we need is public money for clinical tests of disulfiram. And this is, in my opinion, the most important message of our research.

Nonprofit drugsnpd-logo

In the public interest, we need public and/or charitable money. We need disulfiram to get into clinical trials in a nonprofit way. The nonprofit drug development model is, in societies with healthcare based on profit, something totally new. And it well may have the potential to change such healthcare systems globally.

At present, it may seem to be no way to finance clinical trials on large-scale population groups for nonprofit medicines. If there was a way to pay for the trials in a non-commercial way, we could get effective medications that are also very cheap. And in this we see a need for a change in those global healthcare systems, that are dominated by commercial interests.

On this, I wrote in Nonprofit drugs as the salvation for world’s health care systems, published in Drug Discovery Today in 2012, after passing a rigorous review process. In it I also point out that one of the highest incidences of breast cancer occurs in very poor countries, like in Africa, that do not have access to standard oncology treatment.

The argument is very simple. If governments and charities would finance clinical trials of nonprofit drugs, and if these tests were successful, they would help patients all around the world – first of all hundreds of thousands, if not millions, of people in the developing world.

Example of visceral leishmaniasis aka black fever

There is a good example, a drug that was developed in a non-profit way. For curing a disease called visceral leishmaniasis (black fever), a fatal parasitic disease that occurs only in poor regions of India, Bangladesh or Africa.

When researchers found out that this disease could be treated with an “old”, “forgotten” antibiotics paromomycin, Bill and Melinda Gates, together with the World Health Organization and other organizations, agreed to pay for clinical trials. And this medicine works. It helps to cure people, while keeping the price of threating them at a very low level. Curing people of a fatal disease for four euros within three weeks.

There may be a similar opportunity in disulfiram.

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Author: vjr

vjrott.com

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