Fenbendazole, also known as “Fenben,” is a broad-spectrum anthelmintic that has been used in both the human and veterinary fields for nearly six decades. It belongs to a group of drugs called the benzimidazole carbamate anthelmintics, and it has been found to be extremely effective against worms. Fenbendazole is able to kill parasites by binding to their microtubules and disrupting the tubulin microtubule equilibrium. This causes the helminths to lose their motility and disintegrate, leading to apoptosis. In a similar way, fenbendazole also interferes with the function of microtubules in normal mammalian cells by blocking their ability to stabilize themselves.
The effectiveness of fenbendazole for the treatment of cancer is due to its dual mechanism of action, which targets both microtubules and chromatin. The binding of fenbendazole to the microtubules blocks their formation and alters their dynamics, whereas its effects on chromatin are due to its inhibition of the polymerization process that binds dNA to chromosomes. This prevents chromatin from reaching the nucleus, and thereby blocks transcription and replication. The synthesis of dNA by normal cells is then inhibited, and this results in a loss of cell cycle control. The apoptosis that occurs as a result of this loss of cell cycle control results in the death of tumor cells.
In an experiment described in the Table, BALB/cRw mice with EMT6 tumors were randomized at a mean tumor volume of 100 mm3 to serve as untreated controls, or to receive three daily i.p. injections of fenbendazole followed by local tumor irradiation with 10 Gy. Tumor growth curves for the three fenbendazole-treated groups were indistinguishable from those of control tumors. After the mice reached a mean tumor volume of 1000 mm3, they were euthanized and necropsied. No evidence of local invasion or lymph node metastases was observed in any of the animals, nor were a significant number of lung metastases present at necropsy (Table I).
Other experiments have examined the effect of fenbendazole on the radiation response of the EMT6 cells to irradiation and to three daily i.p. injections with fenbendazole given one day before, 2 h before, or one day after irradiation. These studies found no change in either the time to a four-fold increase in volume or the radiation response of the untreated tumors, or the tumor growth or radiation response for the EMT6 tumors treated with three daily i.p. injections and 10 Gy of irradiation.
In these experiments, the cultures were placed in stainless steel pressure bottles and made hypoxic by sealing the lids with rubber gaskets, inserting needles for influx and efflux of gases, and incubating under hypoxia at 37°C for 1 h to produce severe hypoxia. The cultures were then injected with the fenbendazole solution through the septum without breaking the hypoxia and incubated for a further 2 h. Relative surviving fractions were calculated using either the untreated control cultures (for docetaxel alone) or the corresponding fenbendazole-treated cultures from the same experiment for each dose of irradiation. fenbendazole cures cancer