Alcohol-abuse drug Antabuse (disulfiram) kills cancer cells

What the report “Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4” Nature, 6/14 Dec ’17 (1) is all about

“Alcohol-abuse drug Antabuse kills cancer cells”, writes one of the scientists of an international team(1) in a media release of his university (Alcohol-abuse drug Antabuse kills cancer cells,¬†Karolinska Institutet, 7/12 Dec ‚Äô17) about their just published report¬†Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4,¬†Nature, 6/14 Dec ’17(1)¬†and continues that the scientist found out, “that the alcohol-abuse drug Antabuse is effective against cancer [and] identifies a potential mechanism of action for the anti-tumour effect.”

The report is about three issues:

  • The, highly interesting, progress in lab work on disufiram, which “fills an important knowledge gap regarding the anti-cancer mechanism of disulfiram and paves the way for future clinical trials,” as¬†“[in] laboratory experiments, the team found that in mice and in the human body, disulfiram becomes metabolised into a molecule that causes a naturally occurring protein NPL4 to clump together with its partner, the body‚Äôs p97 enzyme. This process ‚Äėfreezes‚Äô and thereby functionally disables the otherwise very mobile and tumour growth-supporting NPL4-p97 duo, resulting in cancer cell death…” (JiŇô√≠ B√°rtek in the Karolinska media release)
    NOTE: the first clinical trial just began in Olomouc(2)
     
  • Yet another¬†analyses/report of the records/cases, this time¬†“of cancer patients across Denmark”. This, I think, may/should be “put into perspective” a bit more thoroughly and together with other cases(3), at least as long as the clinical tests are on the way.
     
  • The Nonprofit drugs issues, briefly mentioned by the authors. This theme, as a larger multidisciplinary project, is currently in preparation(4).
Notes, quotes, further reading

(1)

The countries and institutions of the international team…

  • Czech Rep ‚Äď Palacky University, Olomouc; Charles University, Prague; Psychiatric Hospital, Sternberk
  • Denmark ‚Äď Danish Cancer Society Research Center, Copenhagen
  • Sweden ‚Äď Karolinska Institute, Stockholm
  • Switzerland ‚Äď Kantonsspital St Gallen
  • USA ‚Äď Caltech, Pasadena, California; Wayne State University, Detroit, Michigan; Amgen, Thousand Oaks, California
  • China ‚Äď Guangzhou Medical University, Guangzhou

…and their report:

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
Zdenńõk ҆krott+, Martin MistŇô√≠k+, Klaus Kaae Andersen, S√łren Friis, DuŇ°ana Majera, J√°n Gursk√Ĺ, Tom√°Ň° OŇĺdian, JiŇôina B√°rtkov√°, Zs√≥fia Turi, Pavel Moudr√Ĺ, Marianne Kraus, Martina Michalov√°, Jana V√°clavkov√°, Petr DŇĺub√°k, Ivo Vrobel, Pavla Pouńćkov√°, JindŇôich Sedl√°ńćek, Andrea Miklovińćov√°, Anne Kutt, Jing Li, Jana Mattov√°, Christoph Driessen, Q. Ping Dou, J√łrgen Olsen, Mari√°n Hajd√ļch, Boris Cvek*, Raymond J. Deshaies*, JiŇô√≠ B√°rtek* (+contributed equally, *corresponding authors)
Nature 552, 194‚Äď199 (14 Dec 2017), doi:10.1038/nature25016, published online: 06 Dec 2017

The authors sum up their findings in the report’s last section:

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‚Äďcopper complex (bis (diethyldithiocarbamate)‚Äďcopper)

Discussion
Our results help to explain the anti-cancer activity of the alcohol-abuse drug disulfiram.
We propose a model for DSF cytotoxic activity, featuring rapid conversion of DSF into CuET, which accumulates in tumours. After entering cells, CuET binds NPL4 and induces its aggregation, consequently disabling the vital p97‚ÄďNPL4‚ÄďUFD1 pathway and inducing a complex cellular phenotype leading to cell death (Fig. 4f). Supporting CuET as the active metabolite is the correlation of CuET concentrations (active in the nanomolar range) with the biological effects and functional impact on the targeted pathway(s) in vivo.
In addition, CuET is the only known metabolite of DSF containing copper ions, a metal that enhances the anti-tumour effects of DSF; it is unlikely that another DSF metabolite could represent the major anti-cancer agent as levels of non-CuET metabolites should be lowered by copper addition.
We also present a method for CuET detection in tissues and plasma, as well as data suggesting that preferential accumulation of CuET in tumours may contribute to cancer cell toxicity, consistent with the high therapeutic tolerability of DSF3, as documented even after years of daily administration at doses comparable to those we used in our mouse experiments.
Considering the numerous studies on DSF and diverse opinions about the potential target of its anti-cancer effects44, identification of NPL4, a key component of the p97‚ÄďNPL4‚ÄďUFD1 segregase complex, as the molecular target of CuET is surprising. The CuET‚ÄďNPL4 interaction leads to rapid formation of protein aggregates and immobilization of this otherwise very mobile multifunctional protein complex, resulting in a severe phenotype, induction of HSR and eventually cell death. While additional potential targets of CuET cannot be excluded, the malfunction of the p97 pathway due to the NPL4‚Äďp97 aggregate formation explains the major cell phenotypes and the consequent cell death.
Our work also reconciles the controversial studies6,12, suggesting that the proteasome is the DSF target, by demonstrating that neither 20S nor 26S proteasome, but the processing of ubiquitylated proteins by the NPL4-dependent segregase, is targeted by CuET.
Our results support the notion that the p97‚ÄďNPL4 pathway is a promising therapeutic target in oncology45,46. Indeed, reports on p97 overabundance correlating with progression and metastasis of carcinomas of the breast, colon and prostate47‚Äď49 are consistent with our present nationwide epidemiological analysis, which revealed an association between continued use of DSF and favourable prognosis, an intriguing finding that should be investigated further, particularly given the currently limited therapeutic options for patients with metastatic cancer.
From a broader perspective, our study illustrates the potential of multifaceted approaches to drug repurposing, providing novel mechanistic insights, identification of new cancer-relevant targets and encouragement for further clinical trials, here with DSF, an old, safe and public domain drug4 that might help to save lives of patients with cancer worldwide.


3. Iljin, K. et al. High-throughput cell-based screening of 4910 known drugs and drug-like small molecules identfies disulfiram as an inhibitor of prostate cancer cell growth. Clin. Cancer Res. 15, 6070‚Äď6078 (2009).
4. Cvek, B. Nonprofit drugs as the salvation of the world‚Äôs healthcare systems: the case of Antabuse (disulfiram). Drug Discov. Today 17, 409‚Äď412 (2012).

6. Chen, D., Cui, Q. C., Yang, H. & Dou, Q. P. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 66, 10425‚Äď10433 (2006).

12. L√∂vborg, H. et al. Inhibition of proteasome activity, nuclear factor-őļB translocation and cell survival by the antialcoholism drug disulfiram. Int. J. Cancer 118, 1577‚Äď1580 (2006).

44. Cvek, B. Targeting malignancies with disulfiram (Antabuse): multidrug resistance, angiogenesis, and proteasome. Curr. Cancer Drug Targets 11, 332‚Äď337 (2011).
45. Deshaies, R. J. Proteotoxic crisis, the ubiquitin‚Äďproteasome system, and cancer therapy. BMC Biol. 12, 94 (2014).
46. Anderson, D. J. et al. Targeting the AAA ATPase p97 as an approach to treat cancer through disruption of protein homeostasis. Cancer Cell 28, 653‚Äď665 (2015).
47. Cui, Y. et al. High expression of valosin-containing protein predicts poor prognosis in patients with breast carcinoma. Tumour Biol. 36, 9919‚Äď9927 (2015).
48. Yamamoto, S. et al. Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis. Clin. Cancer Res. 10, 651‚Äď657 (2004).
49. Tsujimoto, Y. et al. Elevated expression of valosin-containing protein (p97) is associated with poor prognosis of prostate cancer. Clin. Cancer Res. 10, 3007‚Äď3012 (2004).


(2)

clinical tests in Olomouc:


(3)

previous, further cases, reports in:


(4)

on Nonprofit drugs see also:

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Disulfiram (Antabuse) against Cancer

Research, Case Reports, Clinical Trials

¬Ľ DEUTSCHAntabuse (disulfiram) against Cancer
a presentation by
 Boris Cvek, Ph.D.
University of Olomouc, Social Health Institute OUSHI
(formerly at the Department of Cell Biology and Genetics)

Research in Cells and Animals

Many scientific publications have demonstrated that Antabuse (disulfiram), especially when combined with copper (cf. The Active Compound further below), kill cancer cells and is able to suppress tumors in mice.

The figure below, from our research now being prepared for publication (Nature, Dec 6/14 2017, doi:10.1038/nature25016, see Alcohol-abuse drug Antabuse (disulfiram) kills cancer cells), shows mice with a metastasis of human breast cancer, most effectively suppressed by the active compound.

antabuse-boris-cvek-01
gluCu = food supplement containing copper | Mock = control group

Case Report by Dr. Lewison (Prog. Clin. Biol. Res. 12, 47-53, 1977)

In 1977, Dr. Lewison from Johns Hopkins University in the USA published a case report of a patient with metastasizing breast cancer who become an alcoholic. Between 1961-1971 she used Antabuse and became cancer-free. She died in 1971 ‚Ästnot because of cancer, but by falling from a window while heavily drunk.

‚ÄúHowever, in 1961 she became a severe alcoholic and it was necessary to discontinue all hormone therapy and Antabuse (Disulfiram) was started¬†[for treatment of alcoholism]. Over the next 10 years ‚Ästfrom 1961 to 1971 ‚Ästcomplete resolution of all bone lesions in the spine, skull, pelvis and ribs gradually occurred and the patient remained clinically free of cancer with no further hormone therapy, chemotherapy, or radiation therapy. Frequent psychiatric care was required and she remained on and off Antabuse therapy for her continued drinking problem. She died in 1971 when she accidentally fell from a third floor window. The coroner’s report showed a high blood alcohol level and residual nests of metastatic carcinoma in the bone marrow.‚ÄĚ

Ditiocarb Clinical Trial (Biotherapy 6, 9-13, 1993)

In 1993, French scientists published a phase II clinical trial of a drug called Ditiocarb. This compound is produced after ingestion of Antabuse. They used very low doses ‚Äď 700 mg weekly, in comparison to a standard Antabuse dosage of 250-500 mg daily.

Sixty-four women with non-metastatic high risk breast cancer after surgery were divided into two equal groups. The first group were placed on standard chemo + placebo, while the second were on the same chemo + Ditiocarb. The drugs were taken for 9 months. After 5 years, 55% of patients were alive in the first group compared to 81% of patients in the second group.

It is to be expected that with higher doses, and after longer treatment, the effect might be much stronger. Our hypothesis is that the active compound (which occurs in the body after Ditiocarb reaction with copper, cf. The Active Compound¬†below) was able to destroy micro metastases in some patients ‚Ästeven at such low doses and after only 9¬†months.

Case Report from Utah (Mol. Cancer Ther. 3, 1049-1060, 2004)

In 2004, scientists from Utah published a case report of a patient with melanoma metastasis in the liver, which ‚Äď by using a combination of disulfiram and zinc ‚Ästshrank after a few months and disappeared after three and a half years.

antabuse-boris-cvek-02

Today, the fact that the active compound is a copper combination is already known (in fact, the zinc compound does not exist in human body and disulfiram prefers copper that is naturally occurring in the body).

Disulfiram Clinical Trial (Oncologist 20, 366-367, 2015)

In 2015, the Oncologist journal published results of a clinical trial from Israel, where 40 patients with metastatic lung cancer were divided into two equal groups (of 20 each). The first group were placed on standard chemo, while the second group were on standard chemo + disulfiram (just 120 mg daily). Patients from the second group survived 3 months longer on average and, most importantly, two survived for a long time. The figure further shows that all the patients from the first group died after two years.

antabuse-boris-cvek-03

The Active Compound

We have various experimental evidence, now prepared for publication, showing that the active compound is a complex of Ditiocarb and copper; which occurs under normal conditions after Antabuse ingestion in the human body.

antabuse-boris-cvek-04

Phase II and phase III clinical trials

To get approval from state authorities for Antabuse to be used normally in oncology, we need to conduct further and larger clinical trials ¬†‚Äď i.e.¬†phase II clinical trials (hundreds of patients) and phase III in particular (thousands of patients). We need such trials to examine various cancers and to combine Antabuse with various standard chemo drugs.

Normally, clinical trials are funded by pharmaceutical companies. However, Antabuse is not patentable. The advantage is that it is affordable (hundreds of Dollars/Euros per patient per year), yet the weakness is that it is not interesting for business. Therefore, Antabuse clinical trials must be paid by charities and governments in the public interest. We want to finance such clinical trials.

If large phase III clinical trials show that Antabuse is able to cure some cancers, it would be, as an inexpensive drug, affordable even for patients in low-income countries.

First Steps and Further Progress ‚Ästincluding fast-track approval

In Olomouc, where we have experience with Antabuse research, there are oncologists who are willing to conduct Antabuse clinical trials. In collaboration with them, we have designed a phase II clinical trial of 100 patients with metastatic breast cancer and 100 patients with metastatic lung cancer (500 mg Antabuse + 2 mg copper daily).

In all patients, overall survival will be determined, and if their tumors shrink, do not grow, or grow further. The results will be of value for the identification of patients who are most sensitive to Antabuse therapy, and for further research as to why some patients are more sensitive than others.

We would also like to conduct further trials in patients with different cancers. In the case of positive results, we would design phase III clinical trials and talk to the FDA and EMA to win a fast-track approval of Antabuse for metastatic cancer where it is curable. Negative results would instigate phase II clinical trials of Antabuse in combination with standard chemo.

Why Test Antabuse in Olomouc?

Those conservative ones among oncologists usually dismiss Antabuse, especially as a drug not developed by big pharmaceutical companies. However, in Olomouc we have a team of oncologists led by prof. Bohuslav Melichar, head of the Oncology Unit of the Teaching Hospital, who are willingto conduct clinical trials of Antabuse in patients with metastatic breast/lung cancer and other cancers ‚Äď as soon as sufficient funding is found.

Cost Estimate of the 100 + 100 Trial

  • Wages of physicians (2 physicians), coordinator and supervisor of clinical trial
    some ‚ā¨ 80,000 per year ‚Äď for 2 years ‚ā¨ 160,000
  • Material (Antabuse, copper supplementation, materials used for standard health care in hospitals), other services and non-material costs (examination of patients, insurance according to law),
    some ‚ā¨ 120,000 per year ‚Äď for 2 years ‚ā¨ 240,000

  • Overall cost of 1 phase II clinical trial of 100 + 100 patients
    some ‚ā¨ 200,000 per year ‚Äď for 2 years ‚ā¨ 400,000

This project is the result of our long-term scientific research of Antabuse anti-cancer activity here in Olomouc. Our experience and concept is (so far) unique to the world. There is only one team, besides us, focused on Antabuse application in oncology, (prof. Weiguang Wang in UK), but they are working on some patentable formulation of disulfiram.

Our strategy is unmatched and fits perfectly into the mission of Olomouc University Social Health Institute (OUSHI). It is not ‚Äúonly‚ÄĚ about curing patients, but we have an ambition to change healthcare systems globally and to make them more affordable with ‚Äúnonprofit drugs‚ÄĚ. Details of this idea can be found in the article ‚ÄúNonprofit drugs as the salvation for world‚Äės health care systems: the case of Antabuse‚ÄĚ by B. Cvek, an OUSHI member, published in the prestigious international scientific journal Drug Discovery Today.


PROJECT HEADS / TEAM ‚Äď Boris Cvek, Ph.D. / prof. Peter Tavel, Ph.D. / et al. (Olomouc University (CZ)

COLLABORATION ‚Äď prof. Ray Deshaies (California Institute of Technology, Pasadena CA (USA) / prof. Vikas Sukhatme (Dana-Farber/Harvard Cancer Research, Boston MA (USA) / prof. Jiri Bartek (Danish Cancer Society Research Center, Copenhagen (DK) / prof. Ping Dou (Barbara Ann Karmanos Cancer Institute, Detroit MI (USA) / prof. Christoph Driessen (Kantonsspital St.¬†Gallen (CH) / prof. Pavla Pouckova (1st Medical Faculty Charles University, Prague (CZ)

Disulfiram (Antabus) gegen Krebs

Forschung, Fallberichte, Klinische Versuche

¬Ľ ENGLISH√úbersetzung von¬†Antabuse (disulfiram) against Cancer
einer Präsentation von Boris Cvek, Ph.D.
Universität Olomouc, Social Health Institute OUSHI
(fr√ľher bei Institut f√ľr Zellbiologie und Genetik)

Forschung an Zellkulturen und Tieren

Viele wissenschaftliche Publikationen¬†haben gezeigt, dass Antabus (Disulfiram), vor allem wenn mit Kupfer kombiniert (vgl. Aktive Verbindung weiter unten), Krebszellen t√∂tet und in der Lage ist, Tumore in M√§usen zu unterdr√ľcken.

Die Abbildung unten zeigt M√§use mit einer Metastasierung von menschlichem Brustkrebs, die die aktive Verbindung (Disulfiram+Kupfer) am effektivsten unterdr√ľckt ‚Äď aus unserer Forschung, die wir gegenw√§rtig zur Publikation vorbereiten (auf Englisch: Nature, Dec 6/14 2017, doi:10.1038/nature25016, siehe auch: Alcohol-abuse drug Antabuse (disulfiram) kills cancer cells).

antabuse-boris-cvek-01
Tag 0 | Tag 32
Disulfiram+Kupfer | Disulfiram | Nahrungsergänzung mit Kupfer | Kontrollgruppe

Fallbericht von Dr. Lewison (Prog. Clin. Biol. Res. 12, 47-53, 1977)

1977 ver√∂ffentlichte Dr. Lewison von der Johns Hopkins Universit√§t in den USA einen Fallbericht √ľber eine¬†Patientin mit metastasierendem Mammakarzinom, die eine Alkoholikerin geworden ist. Zwischen 1961-1971 nahm¬†sie Antabus (Disulfiram) ein und wurde frei von Krebs. Sie starb im Jahre 1971 ‚Ästnicht an¬†Krebs, sondern weil sie, stark betrunken, aus dem¬†Fenster fiel.

‚ÄúDoch 1961 wurde sie zur¬†schweren Alkoholikerin, und es war notwendig, jede¬†Hormontherapie einzustellen und¬†[f√ľr Behandlung des¬†Alkoholismus]¬†mit Antabus (Disulfiram) anzufangen. Im Laufe der n√§chsten 10 Jahre ‚Ästvon 1961 bis 1971 ‚Ästallm√§hlich eine vollst√§ndige Aufl√∂sung aller Knochenl√§sionen in der Wirbels√§ule, im Sch√§del, Becken und den Rippen und die¬†Patientin blieb klinisch frei von Krebs ohne jede weitere Hormon-, Chemo-¬†oder Strahlentherapie. F√ľr ihr anhaltendes Alkoholproblem wurde eine regelm√§ssige psychiatrische Betreuung erforderlich¬†und sie blieb deshalb, auch wenn mit Unterbrechungen,¬†in der¬†Antabus-Therapie. Sie starb im Jahr 1971, als sie zuf√§llig aus einem Fenster im dritten Stock fiel. Der Bericht des Gerichtsmediziner¬†zeigte einen hohen Blutalkoholgehalt auf und residuale Nester von metastasierendem Karzinom im Knochenmark.‚ÄĚ

Klinischer Versuch mit Ditiocarb (Biotherapy 6, 9-13, 1993)

1993 ver√∂ffentlichten franz√∂sische Wissenschaftler eine klinische Phase II Studie mit Ditiocarb. Diese Verbindung wird nach der Einnahme von Antabus im K√∂rper daraus erzeugt. Sie benutzten sehr niedrige Dosen ‚Äst700 mg pro Woche, im Vergleich zu einer Standarddosierung von¬†Antabus von t√§glich 250 bis 500 mg.

Vierundsechzig Patientinnen mit nicht-metastasiertem Hochrisiko-Brustkrebs wurden, nach der Operation, in zwei gleiche Gruppen aufgeteilt (je 32). Die erste Gruppe wurde auf Standard-Chemotherapie + Placebo gesetzt, während die zweite auf die gleiche Chemo + Ditiocarb. Die Medikamente wurden während 9 Monaten eingenommen. Nach 5 Jahren waren 55% der Patientinnen der ersten Gruppe am Leben, im Vergleich zu 81% der Patientinnen der zweiten Gruppe.

Es ist zu erwarten, dass mit h√∂herer Dosierung und nach l√§ngerer Behandlung, der Effekt viel st√§rker sein k√∂nnte. Unsere Hypothese ist, dass der aktive Wirkstoff (der im K√∂rper entsteht, aus¬†Reaktion von¬†Ditiocarb mit Kupfer, vgl.¬†Aktive Verbindung unten),¬†bei einigen Patienten Mikrometastasen zerst√∂rte¬†‚Ästselbst bei so niedrigen Dosierung¬†und nach nur 9 Monaten.

Fallbericht aus Utah (Mol. Cancer Ther. 3, 1049-1060, 2004)

2004 ver√∂ffentlichten Wissenschaftler aus Utah einen Fallbericht √ľber einen Patienten mit Melanom-Metastase in der Leber, die nach¬†Behandlung¬†mit einer¬†Kombination von Disulfiram und Zink nach wenigen Monaten schrumpfte und nach dreienhalb Jahren verschwand.

antabuse-boris-cvek-02
vor Behandlung¬†| mit Behandlung ‚Äď nach 3 Monaten¬†| 10 Monaten |¬†42 Monaten

Heute ist allgemein¬†bekannt, dass die aktive Verbindung die¬†mit Kupfer ist (in der Tat, eine¬†solche Zinkverbindung existiert im menschlichen K√∂rper nicht und Disulfiram bevorzugt Kupfer, das im K√∂rper nat√ľrlich vorkommt).

Klinischer Versuch mit Disulfiram (Oncologist 20, 366-367, 2015)

2015 ver√∂ffentlichte The Oncologist Ergebnisse einer klinischen Studie aus Israel, wo 40 Patienten mit metastasierendem Lungenkrebs in zwei gleiche Gruppen geteilt wurden (von je 20). Die erste Gruppe wurde mit¬†Standard-Chemotherapie behandelt, w√§hrend die zweite Gruppe mit¬†Standard-Chemo + Disulfiram (mit nur 120 mg t√§glich). Patienten aus der zweiten Gruppe √ľberlebten im Durchschnitt 3 Monate l√§nger und, was am wichtigsten ist, zwei f√ľr eine lange Zeit erhalten. Die Abbildung unten¬†zeigt ferner, dass alle Patienten aus der ersten Gruppe nach zwei Jahren gestorben ist.

antabuse-boris-cvek-03

Aktive Verbindung

Wir haben verschiedene experimentelle Beweise, die wir gegenwärtig zur Veröffentlichung vorbereiten, die zeigen, dass der aktive Wirkstoff ein Komplex von Ditiocarb und Kupfer ist; der unter normalen Bedingungen nach Antabus-Aufnahme im menschlichen Körper entsteht.

antabuse-boris-cvek-04

Klinische Studien ‚ÄstPhase II und Phase III

Um eine Genehmigung von staatlichen Beh√∂rden zu erhalten,¬†damit¬†Antabuse in der Onkologie verwendet werden kann, m√ľssen wir weiterf√ľhrende, gr√∂ssere klinische Test durchf√ľhren¬†‚Äď das heisst Phase II der klinischen Tests¬†(Hunderte von Patienten) und insbesondere Phase III (Tausende von Patienten). In diesen¬†Studien¬†werden wir auch¬†verschiedenen Krebsarten und Einsatz von Antabuse untersuchen, kombiniert mit verschiedenen Standard-Chemotherapien.

Normalerweise werden klinische Studien von Pharmaunternehmen finanziert. Allerdings ist Antabuse nicht patentierbar. Der Vorteil dabei ist, dass es erschwinglich ist (pro Jahr Hunderte von Dollar/Euro pro Patient), aber die Schw√§che ist, dass es nicht interessant f√ľr Unternehmen ist. Daher m√ľssen klinische Antabuse Studien von Hilfsorganisationen und Regierungen im √∂ffentlichen Interesse finanziert werden. Wir suchen nach Wegen, wie¬†solche klinischen Studien finanziert werden k√∂nnen.

Wenn die grossen Phase-III-Studien zeigen, dass Antabuse in der Lage ist, einige Krebserkrankungen zu heilen, w√§re es auch, als preiswertes Medikament, erschwinglich f√ľr Patienten in L√§ndern mit niedrigem Einkommen.

Erste Schritte und weiteres Vorgehen ‚Äď einschliesslich¬†Fast-track Zulassung

In Olomouc/Olm√ľtz, wo wir schon Erfahrungen mit der Antabus-Forschung haben, ist ein Onkologen-Team bereit, klinische Studien mit Antabus durchzuf√ľhren. In Zusammenarbeit mit ihnen haben wir eine klinische Phase II Studie von 100 Patienten mit metastasierendem Brustkrebs und 100 Patienten mit metastasiertem Lungenkrebs entwickelt (500 mg Antabus + 2 mg Kupfer t√§glich).

Bei allen Patienten wird das Gesamt√ľberleben ermittelt, und ob ihre Tumore schrumpfen, nicht mehr wachsen oder weiter wachsen. Die Ergebnisse werden wertvoll sein f√ľr Identifizierung von Patienten, die am meisten auf eine Antabus-Therapie ansprechen, wie auch f√ľr weitere Forschung, warum einige Patienten f√ľr sie empfindlicher sind als andere.

Wir w√ľrden auch gerne weitere Studien bei Patienten mit verschiedenen Krebsarten durchf√ľhren. Falls positive Ergebnissen vorliegen, w√ľrden wir klinische Studien der Phase III vorbereiten und sie mit der FDA und EMA er√∂rtern, um eine Fast-track Zulassung von Antabuse zu erreichen, √ľberall wo metastasierender Krebs heilbar ist. Negative Ergebnisse w√ľrden zur klinischen Studien der Phase II f√ľhren von Antabuse in Kombination mit Standard-Chemo.

Warum Antabuse in Olomouc testen?

Die konservativen unter Onkologen nehmen Antabus nicht ernst, vor allem als ein Medikament das nicht von grossen Pharma-Unternehmen entwickelt wurde. Doch in Olomouc haben wir ein Team von Onkologen unter der Leitung von Prof. Bohuslav Melichar, Leiter der Onkologie-Abteilung der Uniklinik, welche bereit sind, klinische Studien mit Antabus bei Patienten mit metastasierendem Brust-/Lungenkrebs und anderen Krebsarten durchzuf√ľhren ‚Äď sobald ausreichende Finanzierung steht.

Kostenschätzung der 100 +100 Tests

  • Lohnsumme der √Ąrzte (2 √Ąrzte), Koordinator und Betreuer der klinischen Studie
    ca. ‚ā¨ 80.000 pro Jahr ‚Äď f√ľr 2 Jahre ‚ā¨ 160.000
  • Material (Antabus, Kupfererg√§nzung, Materialien f√ľr die Standardgesundheitspflege in Krankenh√§usern), sonstige Leistungen und nicht-materielle Kosten (Untersuchungen der Patienten, Versicherung nach Gesetz)
    ca. ‚ā¨ 120.000 pro Jahr ‚Äď f√ľr 2 Jahre ‚ā¨ 240.000

  • Gesamtkosten f√ľr 1 Phase klinischer Studie II von 100 + 100 Patienten
    ca. ‚ā¨ 200.000 pro Jahr ‚Ästf√ľr 2 Jahre ‚ā¨ 400.000

Dieses Projekt ist das Ergebnis unserer langj√§hrigen wissenschaftlichen Forschung der Anti-Krebs-Wirkung von Antabus hier in Olomouc/Olm√ľtz. Unsere Erfahrung und unser Konzept sind (bisher) weltweit einzigartig. Ausser uns gibt es bisher nur ein Team, welches sich auf Antabus-Anwendung in der Onkologie konzentriert (Prof. Weiguang Wang in Grossbritannien), doch sie arbeiten an einer patentierbaren Rezeptur von Disulfiram.

Unsere Strategie ist einmalig und passt perfekt zur Zielsetzung des Social Health Institute (OUSHI) der Universit√§t Olomouc/Olm√ľtz. Selbstverst√§ndlich geht es um Heilung von Patienten, doch nicht “nur”, dar√ľber hinaus wollen wir dazu beitragen, die Gesundheitssysteme weltweit so zu ver√§ndern damit sie wirksame und erschwingliche “gemeinn√ľtzige Medikamente” (“Nonprofit drugs”) zur Verf√ľgung stellen. Details zu dieser Idee finden Sie im Artikel Nonprofit drugs as the salvation for world‚Äės health care systems: the case of Antabuse” (“Nonprofit Medikamente als Rettung f√ľr Gesundheitssysteme der Welt: der Fall von Antabus”) von B. Cvek, OUSHI Mitglied, ver√∂ffentlicht in der renommierten internationalen wissenschaftlichen Zeitschrift Drug Discovery Today.


PROJEKTLEITUNG / TEAM ‚Äď Boris Cvek, Ph.D. / Prof. Peter Tavel, Ph.D. / et al. (Universit√§t Olomouc (CZ)

ZUSAMMENARBEIT ‚Äď Prof. Ray Deshaies (California Institute of Technology, Pasadena CA (USA) / Prof. Vikas Sukhatme (Dana-Farber/Harvard Cancer Research, Boston MA (USA) / Prof. Jiri Bartek (Danish Cancer Society Research Center, Copenhagen (DK) / Prof. Ping Dou (Barbara Ann Karmanos Cancer Institute, Detroit MI (USA) / Prof. Christoph Driessen (Kantonsspital St.¬†Gallen (CH) / Prof. Pavla Pouckova (1st Medical Faculty Charles University, Prague (CZ)