Cancer combination therapies with artemisinin-type drugs

Artemisia annua L. is a Chinese medicinal plant, which is used throughout Asia and Africa as tea or press juice to treat malaria. The bioactivity of its chemical constituent, artemisinin is, however, much broader. We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo. Should artemisinin-type drugs be applied routinely in clinical oncology in the future, then it should probably be as part of combination therapy regimens rather than as monotherapy. In the present review, I give a comprehensive overview on synergistic and additive effects of artemisinin-type drugs in combination with different types of cytotoxic agents and treatment modalities: (a) standard chemotherapeutic drugs, (b) radiotherapy and photodynamic therapy, (c) established drugs for other indications than cancer, (d) novel synthetic compounds, (e) natural products and natural product derivatives, (f) therapeutic antibodies and recombinant proteins, and (g) RNA interference. I also summarize the activity of artemisinin-type drugs towards multidrug-resistant cells and tumor cells with other drug resistance phenomena. As synergistic interactions may not only occur in tumor cells, toxic reactions in normal cells (hepatotoxicity, drug interactions) were also considered. This review summarizes the scientific literature of more than 20years until the end of 2016.