However, in the United States, the drug remains unapproved for use in humans, despite its low toxicity profile in both animals and humans since the 1960s. This inexpensive and efficacious anti-parasitic drug could be useful in treating various cancers, but just like the anti-parasitic drug ivermectin, it too remains suppressed by the Food and Drug Administration and is relegated to being just some "horse dewormer" for veterinary use only.
Multiple peer-reviewed studies show Fenbendazole is a potent anti-cancer drug
In the study, “Repurposing anti-parasite benzimidazole drugs as selective anti-cancer chemotherapeutics (2023),” researchers found that Fenbendazole has two primary mechanisms of action against cancer cells. First, the drug displays anti-mitotic activity, which means it inhibits tubulin polymerization by binding to tubulin sites of rapidly dividing cells. This action causes cell cycle arrest. Secondly, the drug induces oxidative stress that disrupts cell metabolic processes. It inhibits glucose uptake, suppresses key enzymes and reduces the level of available ATP energy, leading to apoptosis of both parasites and cancer cells.
The researchers did however find that benzimidazole drugs have low water solubility, making them hard to apply in clinical applications. This has led researchers to combine the drug with nanoparticles for more effective applications in vivo. There are currently no clinical trials for Fenbendazole, yet there are clinical trials for a similar drug in this class, called Mebendazole. This drug is showing promise as an adjuvant treatment for colon cancer and brain tumors, in combination with other antiprotozoal agents. There is also evidence that benzimidazole drugs sensitize tumor cells so they can become more susceptible to radiation therapy.
In the study, “Anti-cancer effect of fenbendazole-incorporated PLGA nanoparticles in ovarian cancer,” researchers found that fenbendazole’s anti-cancer effects were not realized in mouse models until it was prepared using nanoparticles for efficient drug delivery. The nanoparticles increase the drug’s bio-availability, allowing it to effectively interfere with microtubule polymerization. As the drug blocked cell cycle progression, it increased p53 protein stability and induced apoptosis of the cancer cells. In the end, the drug decreased cell proliferation of both chemo-sensitive and chemo-resistant ovarian cancer cells.
Fenbendazole is effective against breast cancer and chemo-resistant colorectal cancer
In the study, “Redox-mediated Anticancer Activity of Anti-parasitic Drug Fenbendazole in Triple-negative Breast Cancer Cells,” researchers tested fenbendazole on triple negative breast cancer cells, including a highly metastatic type. The drug induced oxidative stress on the cancer cells, making them more vulnerable to apoptosis.
In another 2023 study, the drug was tested on mouse lymphoma and spleen cells to see if there was differentiation between killing cancer cells and preserving healthy spleen cells. The research showed that fenbendazole induces reactive oxygen species and causes cell death of lymphoma cells but does not harm the normal spleen cells. The drug proves to be less toxic to healthy cells than traditional chemotherapy agents, yet similarly lethal to the cancer cells.
In a 2022 study, fenbendazole was tested against chemo-resistant colorectal cancer cells. The researchers found that fenbendazole had six mechanisms of action. The drug triggers apoptosis without affecting p53 expression. It also induces apoptosis by Beclin-1 and causes cell cycle arrest of cancer cells at the G2/M phase. In addition, the drug causes autophagy, necroptosis and ferroptosis, killing off even the most resistant cancer cells.
Fenbendazole can be repurposed to treat human glioblastoma and leukemia
Another study from 2022 provides evidence that benzimidazoles induce apoptosis and pyroptosis of human glioblastoma (GBM) cancer cells. The researchers found that the fenbendazole suppressed DNA synthesis in a dose-dependent manner. Additionally, the drug inhibited cell migration, preventing further invasion of GBM cells. The researchers detailed the direct pathway for which the drug caused programmed cell death in vivo and exactly where it caused cell cycle arrest.
Finally, two studies from 2020 find that benzimidazole could be repurposed into an anti-tumor drug for humans and could be used successfully against leukemia. In the first study, researchers praised benzimidazole for being well tolerated in both animals and humans, with very little side effects. The drugs not only bind to ?-tubulin of parasitic worms, causing their immobilization and death, but they also exert anticancer activities such as: disruption of microtubule polymerization, inhibition of cancer cell viability, migration, invasion and induction of apoptosis and autophagy of cancer cells.
In the other 2020 study, Fenbendazole was specifically found to have anti-cancer activity in HL-60 cells, which are a human leukemia cell line. In a concentration-dependent manner, the drug decreases the metabolic activity and the mitochondrial membrane potential of the leukemia cells. In the end, the drug increased apoptosis and necrosis of the leukemia cells.
With all the promising research on this anti-parasitic drug, there should be no reason to withhold clinical trials for Fenbendazole in the treatment of human cancers.
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