Drug redirection study could identify new treatments for mesothelioma


Research and clinical trials

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The next breakthrough in the treatment of malignant mesothelioma may be on the way.

An international research team based at Temple University in Philadelphia recently identified four drug compounds – already used safely for non-cancerous conditions – that have shown impressive potential for the treatment of mesothelioma. They were part of a new drug redirection project aimed at uncovering much-needed options for mesothelioma patients.

“Mesothelioma has shown resistance to all current treatments, including immunotherapy. New combinations are badly needed now,” Dr. Antonio Giordano, director of the Sbarro Health Research Organization at Temple University, told the Mesothelioma Center on Asbestos.com. “The identification of these compounds suitable for mesothelioma, whose safety has already been evaluated in other diseases, is a very solid starting point.”

Reassignment speeds up the processing process

The use of drug redirection, also known as repositioning, is a strategy that has grown considerably in recent years. It identifies new therapeutic uses for already approved drugs, leading to the fastest possible transition from laboratory to clinic.

Using a drug for a medical condition different from the one for which it was originally developed eliminates most of the risks of developing a new drug from scratch.

“Drug repositioning is an effective and alternative method to traditional drug discovery research and development, which is a well-known, complex, time-consuming and expensive process,” Giordano said. “This is a very important discovery for the treatment of mesothelioma.”

The magazine Cancers published the study which details the findings of the Sbarro Health Research Organization. Stefano Landi and Federica Gemignani from the Genetics Unit of the Department of Biology at the University of Pisa, Italy, participated in the research.

Four drugs will be studied for mesothelioma

What started with 1,170 drug compounds already approved for other human diseases was carefully narrowed down to just four that showed surprising cytotoxic activity, especially with patient-derived malignant mesothelioma cell lines.

These four elements will now be examined more closely both in vitro (in more laboratory tests) and in vivo (in living organisms) before potentially moving on to clinical trials in mesothelioma.

  • Cephalomannin: This anti-tumor compound comes from yew and has shown an ability to block targeted cell growth by stopping cell division.

  • Ouabain: Another plant-derived substance, ouabain is already used in the treatment of congestive heart failure and ventricular arrhythmias. It has also shown promise for leukemia and breast cancer.

  • Thonzonium bromide: This drug has never been considered an anticancer agent. It is an antifungal ingredient used as an additive in ear and nose drops to improve the dispersal and penetration of cellular debris. Its effectiveness was perhaps the biggest surprise.

  • Emetine: Once the drug of choice in the treatment of parasitic infections of the stomach and a home remedy for other gastrointestinal problems, emetine is derived from the root of the ipecac plant.

“We suggest that cephalomannin, ouabain, thonzonium bromide, and emetine might represent novel candidates for reuse to improve the arsenal of therapeutic weapons in the fight against malignant pleural mesothelioma,” the authors wrote. “Once further evidence of their efficacy has been proven, this could be considered for application in a potential combination therapy.”

None of the four drugs have ever been tested against mesothelioma cell lines, according to the study.

Rare cancers benefit most from drug redirection

Drug redirection is particularly important for mesothelioma, a rare cancer with no definitive cure and generally poor prognosis.

Pleural mesothelioma has been treated most successfully with a multidisciplinary approach that includes surgery, chemotherapy, immunotherapy and radiation therapy, but less than a third of those diagnosed are even eligible for surgery.

The average survival time for non-surgical patients is only one year. Various immunotherapy drugs, although often highly touted, have shown mixed results.

Most experts agree that future advances will come from personalized drug combinations, which makes redirection so important.

“That’s why we started fishing through a wide range of repurposed drugs to detect the most active ones, and it is now paramount to investigate the biological mechanisms underlying their activity,” Giordano said.

Researchers seek better treatment options

Repurposing first became popular nearly 30 years ago when scientists began screening the large number of already approved drugs to see if they would work with other medical conditions.

The best-known example of effective drug reuse is Viagra, which was originally developed by Pfizer to treat angina pectoris and hypertension. It was only in later clinical trials that it showed promise for the treatment of erectile dysfunction.

Bringing a new drug to market can take almost 15 years. Reusing medications can cut time in half while dramatically reducing expenses. This is particularly important for rare cancers like mesothelioma, for which research funding is often lacking.

According to the Anticancer Fund, an independent research group that focuses on treating cancer, more than 300 non-cancer drugs have shown evidence of anticancer effects in recent years. Many are being developed for a wide variety of malignancies.

“There is multiple evidence that the one-size-fits-all strategy in cancer treatment is hopeless,” Giordano said. “Identifying specific drugs in the clinical setting must begin with a strong, accurate preclinical study like this.”

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