Cancer accounted for nearly 10 million deaths in 2020 and is the second leading cause of death worldwide. The chemotherapeutic agents that are in clinical practice possess a broad range of severe adverse effects towards vital organs which emphasizes the importance of the discovery of new therapeutic agents or repurposing of existing drugs for the treatment of human
cancers.
Pyrimethamine is an
antiparasitic drug used for the treatment of
malaria and
toxoplasmosis with a well-documented excellent safety profile. In the last 5 years, numerous efforts have been made to explore the anticancer potential of
pyrimethamine in in vitro and in vivo preclinical models and to repurpose it as an
anticancer agent. The studies have demonstrated that
pyrimethamine inhibits oncogenic
proteins such as STAT3, NF-κB, DX2, MAPK, DHFR,
thymidine phosphorylase,
telomerase, and many more in a different types of
cancer models. Moreover,
pyrimethamine has been reported to work in synergy with other
anticancer agents, such as
temozolomide, to induce apoptosis of
tumor cells. Recently, the results of phase-1/2 clinical trials demonstrated that
pyrimethamine administration reduces the expression of STAT3 signature genes in
tumor tissues of
chronic lymphocytic leukemia patients with a good therapeutic response. In the present article, we have reviewed most of the published articles related to the antitumor effects of
pyrimethamine in
malignancies of breast, liver, lung, skin, ovary, prostate, pituitary, and
leukemia in in vitro and in vivo settings. We have also discussed the pharmacokinetic profile and results of clinical trials obtained after
pyrimethamine treatment. From these studies, we believe that
pyrimethamine has the potential to be repurposed as an anticancer drug.