Is Artesunate the Best Partner of Gemcitabine in Pancreatic Cancer?

Pancreatic adenocarcinoma (PDAC) is still one of the most malignant and difficult to treat cancers. The therapeutic protocols in use, such as gemcitabine, gemcitabine associated with nab-paclitaxel and/or cisplatin or the FOLFIRINOX scheme have added very little to PDAC outcome. It is clear by now, that none of them can do the job alone. The more than 3,300 trials registered in clinicaltrials.gov is the best proof that research has not yet found an adequate response to tackle this disease. Thus, an innovative search is badly needed. As part of this investigation we came across a phytotherapeutic product that has been very successful for the treatment of falciparum- and vivax- caused malaria: artemisinin derivatives. These derivatives showed very low toxicity for humans and have been tested in millions of patients with paludism. Interestingly, they have also shown important anti-cancer properties. Regarding PDAC in particular there is strong evidence supporting not only an additive effect to gemcitabine without a concomitant increase in human toxicity, but also decreased resistance. This mini-review will discuss the evidence showing that artemisinin derivatives can be the best possible association with gemcitabine for PDAC chemotherapeutic treatment.