Artemisinin and its derivatives (collectively termed as
artemisinins) are among the most important and effective
antimalarial drugs, with proven safety and efficacy in clinical use. Beyond their
antimalarial effects,
artemisinins have also been shown to possess selective anticancer properties, demonstrating cytotoxic effects against a wide range of
cancer types both in vitro and in vivo. These effects appear to be mediated by
artemisinin-induced changes in multiple signaling pathways, interfering simultaneously with multiple hallmarks of
cancer. Great strides have been taken to characterize these pathways and to reveal their anticancer mechanisms of action of
artemisinin. Moreover, encouraging data have also been obtained from a limited number of clinical trials to support their anticancer property. However, there are several key gaps in knowledge that continue to serve as significant barriers to the repurposing of
artemisinins as effective
anticancer agents. This review focuses on important and emerging aspects of this field, highlighting breakthroughs in unresolved questions as well as novel techniques and approaches that have been taken in recent studies. We discuss the mechanism of
artemisinin activation in
cancer, novel and significant findings with regards to
artemisinin target
proteins and pathways, new understandings in
artemisinin-induced cell death mechanisms, as well as the practical issues of repurposing
artemisinin. We believe these will be important topics in realizing the potential of
artemisinin and its derivatives as safe and potent
anticancer agents.