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

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.