Artemisinin and its derivatives in cancer therapy: status of progress, mechanism of action, and future perspectives

Since the late 1990s, there has been rapid multiplication of data on the anti-cancer properties of artemisinins. This article reviews the status of progress of artemisinin and its derivatives as anti-cancer agents in clinical trials, case reports, and in vitro/in vivo studies. Particular attention is laid on the combinations of artemisinins and synthetic chemodrugs to enhance the latter’s efficacy. An attempt is here made to rationalize the synergistic effects of a few common anti-cancer drugs of the anthracycline, taxane, anti-metabolite, and platinum-based drug families. The various pathways that mediate the action of artemisinins as reported over the past decade are here summarized highlighting also the biomarkers that could be used to better predict the efficacy of the sesquiterpenoids. Their main action seems to be directed toward stalling tumor cell proliferation through cell cycle arrest mediated by reactive oxygen species (ROS). The emergence of artemisinins’ nano-based formulations in combination with chemodrugs to enhance drug bioavailability and targeting as well as immunotherapy is also reviewed. The enhanced efficacy of artemisinin dimers compared to the parent molecules and standard chemotherapy is analyzed. While these therapies hold promises, it may be premature to conclude on their efficacy in the absence of clinical studies.