Anticancer drug repositioning against tropical diseases: The example of methotrexate in the treatment of malaria

In Africa, current antimalarial strategies rest on the use of the artemisinin combination therapies (ACTs). However, resistance to artemisinin has emerged in South East Asia, and experience indicates that this resistance would eventually reach Africa, a scenario that would be associated with increased malaria morbidity and mortality. Thus, more than ever, new drugs are urgently needed. One of the strategies to discover new drugs is to reposition or repurpose existing drugs, thus reducing the cost and time of drug development. For instance, some anticancer drugs (anticancers) such as methotrexate are potent against malaria. However, anticancers are commonly perceived to be too toxic, thus not suitable for malaria treatment. In this chapter, we examine (1) how the toxicity of anticancers is just a matter of dose or only dose makes the poison, as coined in Paracelsus' Law; (2) and the potential of the anticancer methotrexate to treat malaria, thus demonstrating that the opportunity exists to discover new antimalarials using the anticancer pharmacopoeia.