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Cardiac glycosides in cancer therapy: from preclinical investigations towards clinical trials

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Summary

Cardiac glycosides have a long history in the treatment of cardiac disease. However, several preclinical studies as well as two phase I studies have shown that cardenolides may also possess anticancer effects. The mechanisms of these anticancer effects may include intracellular decrease of K+ and increase of Na+ and Ca2+; intracellular acidification; inhibition of IL-8 production and of the TNF-α/NF-κB pathway; inhibition of DNA topoisomerase II and activation of the Src kinase pathway. To date three cardiac glycosides have been developed for treatment of cancer and were tested in a phase 1 clinical trial to determine dose limiting toxicities and maximum tolerated dose. Future studies of this novel class of anticancer drugs are warranted to determine their possible role in cancer treatment.

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Acknowledgments

C. Cerella is supported by a “Waxweiler grant for cancer prevention research” from the Action LIONS “Vaincre le Cancer”. Research at LBMCC is financially supported by the Fondation de Recherche Cancer et Sang, the Recherches Scientifiques Luxembourg association, the Een Haerz fir kriibskrank Kanner association, the Action Lions Vaincre le Cancer association, the European Union (ITN “RedCat” 215009, interreg Iva project “Corena”) and the Télévie Luxembourg. Marc Diederich is supported by the National Research Foundation (NRF) by the MEST of Korea for Tumor Microenvironment Global Core Research Center (GCRC) grant, [grant number 2012-0001184]; by the Seoul National University Research grant and by the Research Settlement Fund for the new faculty of SNU.

Conflict of interest

C. Cerella is supported by a “Waxweiler grant for cancer prevention research” from the Action LIONS “Vaincre le Cancer”. Research at LBMCC is financially supported by the Fondation de Recherche Cancer et Sang, the Recherches Scientifiques Luxembourg association, the Een Haerz fir kriibskrank Kanner association, the Action Lions Vaincre le Cancer association, the European Union (ITN “RedCat” 215009, interreg Iva project “Corena”) and the Télévie Luxembourg. M. Diederich is supported by the National Research Foundation (NRF) by the MEST of Korea for Tumor Microenvironment Global Core Research Center (GCRC) grant, [grant number 2012-0001184]; by the Seoul National University Research grant and by the Research Settlement Fund for the new faculty of SNU.

The other authors declare that they have no conflict of interest.

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Slingerland, M., Cerella, C., Guchelaar, H.J. et al. Cardiac glycosides in cancer therapy: from preclinical investigations towards clinical trials. Invest New Drugs 31, 1087–1094 (2013). https://doi.org/10.1007/s10637-013-9984-1

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