The process of developing novel anticancer agents has become more costly and lengthy than ever1. In addition, agents that target de novo pathway not only put the patients to unpredictable toxicity but also increase the risk in drug development2. Therefore, re-discovering the potential of decade-old drugs for novel anticancer therapeutics provides a new route for drug development. Thalidomide, rapamycin, and azacitidine exemplify the potential of this approach and many more, such as metformin, and valproic acid are in the process of validating their role as new anticancer agents3, 4. Now we have two more members to join the rank. Cardiac glycosides, which have been used to treat cardiac failure for decades, recently emerge as potential anti-cancer agents5. A recent work by TAILLER et al took advantage of high thorough-put screening of 1040 FDA approved agents for antileukemic activity and identified ouabain and zinc pyrithione, which have been used in the past for treating heart failure and dermatologic diseases respectively, as novel antileukemic agents6. They found that these agents induced apoptosis of various leukemic cells through the inhibition of NF-κB pathway. Although these two agents induce apoptosis of leukemic cells through common downstream signal pathway, how they differ in upstream remains elusive. For clarity of discussion, we here focus on the potential of cardiac glycosides.

The notion of using cardiac glycosides for its potential anticancer activity has been around for several decades, due to observation that breast cancer patients with digitalis therapy tends to have lower recurrence7, 8. Some even suggests that the association of high plasma level of digitoxin with reduced risks for cancer9. Using cardiac glycosides for anticancer treatment has a sound mechanistic basis. First, essentially all types of cancer cells have aberrant metabolisms (called Warburg effect) that can be differentiated from normal cells, making cancer metabolism an ideal target for drug development. Second, the toxicity of cardiac glycosides has been well characterized. Thus, the toxicity and cost might be more predictable for the development of this class of drugs. There have been several clinical trials testing the potential of cardiac glycosides, alone or in combination with chemotherapy, for various cancers10, 11.

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