Modern medicine continues to wrestle with the threat posed by cancer. Despite the addition of targeted therapies, immunotherapy, and precision medicine, developing new cancer drugs remains difficult, expensive, and time-consuming. In fact, the average time and cost to develop and gain approval for a new drug is over a decade and billions of dollars. Because of these difficulties, researchers are turning to a new method called drug repurposing, which involves finding new therapeutic uses for already existing medications.
Recent studies have sought to identify potential anticancer activity in several non-oncology drugs. Numerous studies have analyzed compounds, especially noted are the studies of fenbendazole vs mebendazole and the effects certain antiparasitic drugs may have on cancer-associated biological pathways. In the medical community, there is great interest in the potential of previously approved drugs to be incorporated into cancer therapy, whether used by themselves, or in combination with existing therapies.
What is Drug Repurposing?
Drug repurposing, or drug repositioning, is the process of finding new uses for drugs that have already been approved for other medical conditions. In contrast to conventional drug discovery and development, which is focused on developing new compounds, drug repurposing relies on drugs for which the safety and pharmacological profiles are well-established.
This strategy comes with a number of benefits:
- Development time is shortened as existing medications have already gone through the testing phase.
- Less funding is needed as several preliminary testing phases may be skipped.
- Success rates increase as the knowledge of the drug’s pharmacy reduces risk in the clinical trial.
There is also an opportunity to create combination therapies because existing medications that are repurposed can be used with existing medications for the treatment of cancer.
Considering all of these benefits, it is easy to understand why drug repurposing is a strategy greatly sought after by researchers in the field of oncology. In laboratory and preclinical studies, the anticancer effects of existing drugs have been discovered, and researchers have hundreds more to test.
Why is drug repurposing important in oncology?
To answer this question, it is important to understand that oncology is not simply the study of cancer because cancer itself is not simply a single, isolated disease. Cancer is made up of several different disorders and is characterized by uncontrolled cellular growth, genetic mutations, and a complex web of signaling pathways. One of these pathways is developed resistance to therapies that are proven to be effective, which creates a problem of treatment as the disease progresses.
In this context, repurposed medication may provide new methods in which to approach the treatment of cancer by appropriately targeting these pathways. A number of other disease treatments have been found to influence and modify a number of processes that are critical to cancer, such as cellular division, metabolism, and the immune response.
An example of this are some of the drugs used to treat parasitic infections of the class known as benzimidazoles. There is a great deal of interest in these drugs because of their ability to bind to and modify a type of cellular structure known as microtubules, which are critical to the process of cellular division. The ability of these drugs to alter microtubules may be useful for slowing or even preventing the uncontrolled proliferation of cancer cells.
Antiparasitic Drugs and Cancer Research
One class of drugs that is often studied for repurposing is anthelmintics, which are drugs that were first designed to treat infections caused by parasitic worms. Some drugs in this class have been shown to cause the death of cancer cells in vitro.
One example is mebendazole, which has been studied for its potential to reduce cancer. Some studies show that this drug stops tubulin polymerization, a cell division process, and thus causes cancer cells to be arrested in mitosis and die by apoptosis.
Some studies have shown that mebendazole can reduce the growth of the following types of cancer:
- Brain cancer, specifically glioblastoma
- Colorectal cancer
- Lung cancer
- Melanoma
- Ovarian cancer
This suggests that mebendazole causes the modulation of several different signaling pathways that are important for the development and spread of cancer.
Another example is fenbendazole. This drug is similar to mebendazole and is used only in the treatment of animals. It has been used in preclinical studies and shows promise for disrupting the formation of microtubules, which in turn leads to a disruption in the metabolism of cancer cells and that can ultimately reduce the growth of tumors in different experimental models.
Working Mechanisms of Repurposed Drugs
There are multiple possible ways in which repurposed drugs may affect cancer biology. While the specific impacts can be different from one compound to the other and from one type of cancer to the other, there are some pathways that are widely recognized.
Interruption of Cell Division
Some of these drugs can affect the microtubule scaffolding system and interfere with the ability of the cell to replicate. If the cell is not able to divide, the cancer cell may die.
Suppression of Tumor Cell Metabolism
To grow and spread, cancer cells are very energy demanding. Some repurposed drugs can affect the cell’s interstitial metabolism, thus reducing the supply of glucose or other energy sources that the tumor cells need.
Interruption of Signaling Pathways
Cancers are very dependent on certain signaling pathways like MAPK, STAT, and Hedgehog pathways. Some repurposed drugs can interfere with these signaling pathways and therefore limit the growth of the tumors.
Improvements of Current Treatments
A very interesting approach is the use of repurposed drugs in combination with chemotherapy or targeted therapies. For instance, studies in the lab have demonstrated that mebendazole can improve the potency of chemotherapy by causing increased death of cancer cells.
Barriers and Challenges
Above all, there are challenges that the repurposing of drugs in oncology still presents.
First, a lot of studies done in a laboratory or using animals instead of doing extensive human clinical trials. These studies can provide some valuable information, but don’t always turn into effective treatments.
Second, dosing strategies and how a drug acts in the body can differ a lot between the original indication and the proposed use in cancer. An infection treatment may have safe dose levels, but studies in cancer may require different dosing strategies.
Third, even with one indication, one can still encounter the complexity of regulatory approval. Because a drug is approved for one indication, that does not mean that proving the drug is effective for cancer will not require the usual extensive clinical studies and scientific proofs.
The source of this information is Dr Gina SIms.
The Future of Drug Repurposing in Cancer Research
The fields of computational biology, artificial intelligence, and systems medicine have propelled the field of drug repurposing research. For the first time, modern data analyzing techniques can aid scientists in finding the intersection of drugs, genes and biological systems of diseases.
Network-based methods are a prime example of how one can study the interactions of proteins and cellular signaling systems to understand how certain existing drugs may alter the mechanisms of different and specific types of cancer. These methods greatly outperform the traditional way of selecting drugs to study. The area of drug repurposing is aided by joint research projects undertaken by Universities and Collaborating Partners from the Pharmaceutical and Biotech Industries. While the scientific community works for new drug combinations and new treatment strategies, the number of clinical trials using repurposed drugs continues to rise.
Conclusion
An increasingly promising and more creative approach to the search for effective treatments for cancer is drug repurposing. By finding new uses for old drugs, researchers may be able to shorten the time required to bring new drug treatments to the market and provide health care professionals more options to treat patients.
Some biological effects encountered in laboratory studies are very interesting and justify further study. The antiparasitic drugs fenbendazole and mebendazole were originally developed for parasitic infections and are of particular interest. While research comparing fenbendazole and mebendazole is ongoing, most of the evidence is preliminary and needs to be validated by clinical studies.
