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Treatment of Chemotherapy-Resistant Small Cell Lung Cancer

Ref-Nr: TA-P-1306


Kurzfassung

Lung cancer is the leading cause of death among men and women in North America and attracts substantial pharmaceutical investment. However, in contrast to non-small cell lung cancer (NSCLC) therapies, where significant progress has been made with targeted agents and immunotherapies, the small cell lung cancer (SCLC) landscape has remained static for more than 30 years. However, we have shown that cyclodextrin stimulates the anti-tumor effect of combinations of disulfiram with various heavy metal salts. Surprisingly, the tested T-cell lymphoma/leukemia, carcinoma, non-T-cell leukemia and SCLC cells are hypersensitive to the combination treatment in cyclodextrin formulation.


Hintergrund

Lung cancer is the leading cause of death among men and women in North America and attracts substantial pharmaceutical investment. However, in contrast to non-small cell lung cancer (NSCLC) therapies, where significant progress has been made with targeted agents and immunotherapies, the small cell lung cancer (SCLC) landscape has remained static for more than 30 years. SCLC has been fittingly referred to as “a graveyard for drug development”. However, we have shown that cyclodextrin stimulates the anti-tumor effect of combinations of disulfiram with various heavy metal salts. A clear synergistic anti-tumor effect of cyclodextrin with disulfiram/ aurothiomalate was shown in 10 different human cancer cell lines. The spectrum of anti-tumor activity of aurothiomalate/disulfiram in cyclodextrin formulation was evaluated in various cell types. Synergisms between disulfiram and aurothiomalate can be observed in cyclodextrin formulation in all tested cells. This effect differs from one cell line to the other by up to 4 orders of magnitude. Surprisingly, the tested T-cell lymphoma/leukemia, carcinoma, non-T-cell leukemia and SCLC cells are hypersensitive to aurothiomalate/disulfiram treatment in cyclodextrin formulation.


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Lösung

The present technology provides combinations and pharmaceutical compositions comprising a dithiocarbamate such as disulfiram and cyclodextrin, with a source of a heavy metal. Surprisingly, we found a synergistic potentiation of the anti-tumor effect when a dithiocarbamate/heavy metal mixture was combined with a cyclodextrin. The combination is particularly useful in the treatment of tumor diseases and other disorders. 


Vorteile

  • Treatment of SCLC

Anwendungsbereiche

  • Pharmaceutical composition
  • Treatment 

Deutsches Krebsforschungszentrum DKFZ

Dr. Dirk Kuck
06221-42-2945
d.kuck@dkfz.de
www.dkfz.de
Adresse
Im Neuenheimer Feld 280
69120 Heidelberg



Entwicklungsstand

Erste Wirksubstanz


Stichworte

SCLC, combination therapy, heavy metal, Therapeutics

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