Flubendazole Plays an Important Anti-Tumor Role in Different Types of Cancers

Abstract

Flubendazole, belonging to benzimidazole, is a broad-spectrum insect repellent and has been repurposed as a promising anticancer drug. In recent years, many studies have shown that flubendazole plays an anti-tumor role in different types of cancers, including breast cancer, melanoma, prostate cancer, colorectal cancer, and lung cancer. Although the anti-tumor mechanism of flubendazole has been studied, it has not been fully understood. In this review, we summarized the recent studies regarding the anti-tumor effects of flubendazole in different types of cancers and analyzed the related mechanisms, in order to provide the theoretical reference for further studies in the future.

Identification of Promising Drug Candidates against Prostate Cancer through Computationally-Driven Drug Repurposing

“…Moreover, it also strongly upregulates the expression of p53 and its downstream effector p21, which are genes frequently mutated in several types of cancer [ 189 ]. Of note, Flubendazole has been found to exert synergistic effects with 5-fluorouracil against CRPC in PC-3 xenograft models [ 137 ], and it has been reported to exert anti-tumor effects on different types of cancers [ 190 ]. Notably, this compound is closely related to mebendazole, another anthelmintic drug that has recently been repurposed in combination with docetaxel against prostate cancer [ 191 ].…”

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

“…The use of approved drugs able to modulate the expression and function of the immune checkpoint could represent an interesting option to promote efficacy of anti-PD-1/PD-L1 antibodies. Small molecules specifically targeting the checkpoint are being designed and developed, but the full development process is long (>10 years in most cases), excessively costly (about 1.5 b$/molecule), and at a high risk of failure [ 108 , 144 ]. The repositioning of an approved drug may be a more rapid and less risky alternative than the de novo development of a novel chemical entity.…”

“…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 ]. We only focus on the capacity of this compound to modulate the PD-1/PD-L1 checkpoint.…”

“…The drug has shown efficacy in models of breast, lung, and skin cancers, and cancer of the oral cavity. Its mechanism of action is multifactorial, including cell cycle effects, a decrease in cancer cell stemness, suppression of cancer cell proliferation and induction of apoptosis, inhibition of cell migration, modulation of drug resistance, and, importantly here, silencing of the immune suppressive effects of PD-1 [ 108 , 109 ]. Li and coworkers [ 110 ] demonstrated that FLU inhibited the tumoral expression of PD-1, but not PD-L1, and the effect was concomitant to a drug-induced down-regulation of phospho-STAT3 in the tumor tissue.…”

Chemical and pharmacological characterization of anthelmintic benzimidazoles

“…A tumorellenes szinergizmus létrejöhet a benzimidazolok és többek között a temozolomid, fluorouracil, docetaxel, paclitaxel, gemcitabin, ciszplatin és trametinib együttes adagolása révén. Ezáltal a hatóanyagcsoport fontos adjuváns lehet a hagyományos terápiára rezisztens esetekben [42][43][44][45][46][47][48].…”