Despite cancer emerging as a significant cause of mortality, progress in finding novel drugs to treat the condition has been slow. Chemotherapy, radiotherapy, and surgical removal of cancer cells remain the mainstay of cancer treatment.
Chemotherapy, another name for drug therapy, has a unique role in cancer treatment, as unlike radiotherapy or surgery, medications can help overcome widespread cancer. However, most traditional cancer drugs suffer from severe side effects, as they are toxic to healthy cells too. Anticancer drugs are expensive and take an extremely long time to develop.
It is not uncommon in medicine to find out or discover some new effects of the already existing drugs, like the use of low-dose aspirin for preventing heart attack. Similarly, science has identified many medications that are already in use for treating various ailments to possess anticancer activity. Such discoveries not only have the potential for improving cancer treatment, but they also reduce the time required to introduce new anticancer drugs.
A recent scientific report published in the reputed journal “Nature” indicates that one of the common and inexpensive anthelminthic drugs may have a role in cancer treatment.
Fenbendazole – a well-known anthelminthic drug may help treat cancer
Fenbendazole is a well-known broad-spectrum anthelminthic/antiparasitic drug that is widely used in veterinary medicine. It has a wide safety margin and is known to be safe in a number of species, including humans.
Unlike traditional anticancer drugs, it has very low toxicity. Now the latest research shows that it may help kill cancer cells and thus treat cancer. It acts on cancer cells in a number of ways leading to the apoptosis (programmed cell death) of cancer cells.
Fenbendazole help kill cancer cells in multiple ways
Fenbendazole targets or polymerizes cellular microtubules. Microtubules are unique kinds of proteins that play an important role in various functions of body cells, especially in fast-growing cells like cancer cells. Microtubules are required for cell structures, transportation of essential nutrients, the formation of DNA, and so on. Fenbendazole prevents cancer cell growth and even causes the death of cancer cells by affecting microtubules.
Targeting microtubules, a kind of cellular protein, is not new in cancer therapy. Many well-known cancer drugs do that, like vinca alkaloids (vinblastine, vinflunine, etc.), colchicine, paclitaxel, docetaxel, discodermolide. Tubulin-binding drugs kill cancerous cells by inhibiting microtubule dynamics, which are required for DNA segregation and therefore cell division. low drug concentrations suppress both dynamic instability (inhibits mitosis and cancer growth rates) and cell migration,
Researchers found that the effect of fenbendazole on cellular microtubules was partial and milder when compared to other anticancer drugs like nocodazole and colchicine. This may explain much lower toxicity of fenbendazole in comparison to these drugs.
Interestingly, researchers also found that unlike taxanes (paclitaxel) and vinca alkaloids, fenbendazole does not affect the expression of p-glycoprotein. Patients given taxanes or vinca alkaloids frequently become resistant to these and many other drugs due to their effect on p-glycoprotein. This means that there is a much lesser chance that cancer cells may develop resistance to fenbendazole over the long run, and neither it will cause resistance to other cancer drugs.
Fenbendazole seems to have a catastrophic effect on the growth of cancer cells. It prevents their multiplication via mitosis and may accelerate the death of existing cancer cells in a programmed manner. In the latest study on cancer cells in the lab, as much as ~30% of cancer cells died after 32 hours of treatment with fenbendazole. This experiment was done on a highly aggressive kind of cancer cells called non-small cell lung carcinoma (NSCLC).
Fenbendazole may also help enhance the accumulation of p53, a kind of protein that helps regulate a cellular life cycle and prevent the development of cancer cells in humans. This is another way in which fenbendazole may exert its anticancer effect.
Cancer cells grow faster than healthy cells, and they are energy-hungry. This also means that they can be more readily starved by using drugs that affect energy metabolism. Fenbendazole seems to inhibit glucose uptake by cells in a number of ways, it may influence receptors or gateways involved in glucose metabolism (GLUT-4), and may also inhibit working of various glycolytic enzymes (enzymes that break glucose for energy) like Hexokinase II. When cancer cells fail to get enough energy to maintain their high rate of metabolism, they tend to die. This effect is not seen on healthy cells as their energy needs are much lower than cancer cells.
This means that fenbendazole acts on cancer cells in multiple ways; by targeting microtubules, affecting cellular lifecycle, having an impact on cellular metabolism, especially on glucose metabolism, and so on. Various modes of action on cancer cells mean that there are minimal chances for cancer cells to develop resistance to the drug. It also means that fenbendazole, both due to its more or less unique mode of action and lower toxicity, can be combined with other anticancer drugs.
Combination of fenbendazole with other anticancer drugs
Most cancer treatments require therapy with multiple medications to eradicate the disease and prevent resistance. Fenbendazole, if used alone, will not be enough for treating cancer. Fortunately, research indicates that it can be safely combined with various anticancer medications.
The latest study looked into the benefits of combining fenbendazole with other chemotherapy medications targeting microtubule like dichloroacetate (DCA), glycolytic inhibitor 2 (2DG), and so on. In the study, fenbendazole showed strong synergism with DCA or 2DG. Meaning that when it was used along with these anticancer drugs, the effectiveness of anticancer therapy increased by multiple times.
To conclude, fenbendazole acts through microtubule disruption, p53 stabilization, and interference with cellular glucose metabolism, which finally results in accelerated elimination of cancer cells. Since fenbendazole is already proven to be safe for use in humans and is readily available, there is clearly a need for more extensive clinical trials with the medication to ensure that it could be added to the arsenal of anticancer therapy at earliest.