Antiparasitic agents in oncology: Innovative mechanisms, emerging evidence and clinical potential in cancer treatment

The repurpose of established antiparasitic agents for oncological applications represents a promising and cost-effective strategy in the search for novel anticancer therapeutics. Drugs originally developed to treat parasitic infections, including ivermectin, mebendazole, niclosamide, albendazole, artesunate, flubendazole, and other antiparasitic agents, have demonstrated compelling anticancer properties across a wide range of preclinical models. Their mechanisms of action are multifaceted, encompassing disruption of microtubule dynamics, induction of apoptotic signaling cascades, inhibition of key oncogenic pathways (including Wnt/β-catenin, PI3K/Akt/mTOR, and Hedgehog signaling), immunomodulation, and targeting cancer stem cell populations. Ivermectin, a macrocyclic lactone, has shown potent activity against breast, ovarian, and colorectal cancer models through modulation of the P-glycoprotein drug efflux pump, activation of chloride ion channels, and inhibition of oncogenic signaling. Mebendazole, a benzimidazole antiparasitic, exerts anticancer effects primarily through inhibition of tubulin polymerization, mirroring mechanisms of conventional taxane and vinca alkaloid chemotherapeutics, and has additionally demonstrated anti-angiogenic and immunostimulatory properties. Emerging preclinical and early clinical data support anticancer activity for niclosamide (STAT3/Wnt inhibitor), artesunate (reactive oxygen species induction), and pyrvinium pamoate (Wnt pathway blockade). Despite substantial in-vitro and in-vivo evidence, the clinical translation of these agents faces significant challenges, including pharmacokinetic limitations, heterogeneous dosing regimens, and the paucity of adequately powered randomized clinical trials. This review systematically examines the current mechanistic understanding, experimental evidence, and clinical data supporting the repositioning of antiparasitic drugs as anticancer agents, while critically evaluating the limitations of existing evidence and outlining future research priorities.