Double Repositioning: Veterinary Antiparasitic to Human Anticancer

Abstract

Drug repositioning, the approach of discovering different uses for existing drugs, has gained enormous popularity in recent years in the anticancer drug discovery field due to the increasing demand for anticancer drugs. Additionally, the repurposing of veterinary antiparasitic drugs for the treatment of cancer is gaining traction, as supported by existing literature. A prominent example is the proposal to implement the use of veterinary antiparasitics such as benzimidazole carbamates and halogenated salicylanilides as novel anticancer drugs. These agents have revealed pronounced anti-tumor activities and gained special attention for “double repositioning”, as they are repurposed for different species and diseases simultaneously, acting via different mechanisms depending on their target. As anticancer agents, these compounds employ several mechanisms, including the inhibition of oncogenic signal transduction pathways of mitochondrial respiration and the inhibition of cellular stress responses. In this review, we summarize and provide valuable information about the experimental, preclinical, and clinical trials of veterinary antiparasitic drugs available for the treatment of various cancers in humans. This review suggests the possibility of new treatment options that could improve the quality of life and outcomes for cancer patients in comparison to the currently used treatments.

Structural Changes, Biological Consequences, and Repurposing of Colchicine Site Ligands

“…Benzimidazole anti-parasite CBSIs have shown activity against multiple cancers, both in mice and in humans, and consequently are the subjects of numerous studies aiming to repurpose these compounds for the therapy of human cancers [32][33][34][35]. The results of these studies have demonstrated their activity against brain tumors, which was first observed in mouse models of glioma and medulloblastoma being treated with mebendazole for worm infestations [36].…”

“…Subsequent studies have indicated the activity of these compounds against a variety of cancers, including brain, head and neck, breast, colorectal, lung, ovary, prostate, pancreatic, and liver, due to their involvement in multiple mechanisms, including microtubule dynamics, signal transduction, glycolytic/oxidative metabolic balance, glucose uptake, anti-angiogenesis, and others [37][38][39][40]. A number of benzimidazoles have shown anticancer activity, notably mebendazole [34,35], but also albendazole [38], flubendazole [32], fenbendazole [41], parbendazole [39], and others [33,39]. Their activity has been studied both as monotherapy and in combination with standard therapy [33,34].…”

Drug Repurposing to Enhance Antitumor Response to PD-1/PD-L1 Immune Checkpoint Inhibitors

“…In addition to their primary antiparasitic effects, most of these benzimidazole derivatives have revealed interesting anticancer properties, which has encouraged the design of benzimidazole-containing anticancer drugs [ 104 ] and the repositioning of these antiparasitic drugs for the treatment of cancer. The anticancer properties of drugs such as albendazole and fenbendazole have been amply reported [ 26 , 105 , 106 ]. The most potent compound in the series is certainly flubendazole (FLU) [ 107 , 108 ].…”

Exceptional Repositioning of Dog Dewormer: Fenbendazole Fever

“…In addition, several antiparasitic drugs that have been in clinical use for decades have been investigated for repurposing in oncology [ 9 ]. The repositioning of anthelminthic pleiotropic benzimidazole carbamate (BZ) group drugs such as MBZ, albendazole (ABZ), and flubendazole has recently opened new avenues in cancer treatment owing to their easy access, low cost as generic drugs, and safety in human application [ 10 , 11 ]. Another potent and efficient pharmacological candidate from this group for repurposing as an anticancer drug is fenbendazole (FZ), which is widely used in veterinary medicine to treat parasitic worms including ascarids, whipworms, hookworms, and a single species of tapeworm, Taenia pisiformis , in humans and animals [ 12 ].…”