Repurposing of Anthelminthics as Anticancer Drugs
Society of Research on the Biology and Treatment of Cancer, A-1160 Vienna, Austria
Repurposing refers to the reuse of conventional drugs with distinct indications for new applications in order to speed up drug development by capitalizing on previous knowledge and safety data. A prominent example is the proposal to implement anthelminthics, such as mebendazole, niclosamide and pyrvinium pamoate, as novel anticancer drugs. Numerous studies have demonstrated activity of these agents against a wide variety of cancers, especially cancer stem cell-like subpopulations, by a host of different mechanisms which comprise inhibition of signaling pathways, of mitochondrial respiration, as well as of cellular stress responses and others. However, these anthelminthics were administered orally for the treatment of nematode infections and showed mostly poor resorption and, therefore, systemic toxicity data are frequently not available. Furthermore, the host of different targets described seems to be linked to the capability of the benzimidazoles (mebendazole), salicylanilides (niclosamine) and cyanine dye derivatives (pyrvinium) to interact with DNA directly. In conclusion, anthelminthics poorly fulfill the preconditions of a specific mode of anticancer action and availability of pharmacokinetic and pharmacodynamic data for a favorable repurposing as anticancer drugs.
Keywords: Anticancer drug, anthelminthics, repurposing, mebendazole, niclosamide, pyrvinium.