Researchers at Queen Mary University of London have developed a breakthrough treatment for malignant mesothelioma that significantly extends patients' survival by combining a new drug, ADI-PEG20, with chemotherapy. This innovative approach brings new hope to a disease with limited treatment options and has the potential to change the treatment landscape for other cancers.

An innovative treatment significantly improves survival rates for patients with malignant mesothelioma, a rare and rapidly fatal cancer with limited effective treatments, according to results of a clinical trial led by Queen Mary, University of London.

This Phase 3 clinical trial, led by Professor Peter Szlosarek of Queen Mary University and sponsored by Polaris Pharmaceuticals, reveals a breakthrough in the treatment of malignant pleural mesothelioma (MPM).

The ATOMIC-meso trial, a randomized placebo-controlled study of 249 patients with MPM, found that a treatment that combined the new drug ADI-PEG20 with traditional chemotherapy extended participants' median survival by 1.6 months and quadrupled survival by 36 months compared with placebo chemotherapy.

This finding is significant because MPM has the lowest 5-year survival rate of all solid tumors, only around 5-10%. This innovative approach marks the first time in 20 years that chemotherapy has been successfully combined with a drug that targets cancer metabolism to treat the disease.

MPM is a rare, aggressive cancer that affects the lining of the lungs and is linked to asbestos exposure. Treatment is usually with powerful chemotherapy drugs, but these drugs rarely stop the progression of the disease.

The science behind treatment

The premise of this new drug treatment is simple: cut off the tumor's food supply, starving it. All cells require nutrients, including amino acids like arginine, to grow and reproduce. ADI-PEG20 works by depleting arginine levels in the blood. For tumor cells that are unable to make arginine because of a missing enzyme, this means their growth is stunted.

Professor Szlosarek discovered that malignant mesothelioma cells lack a protein called ASS1, which allows the cells to make their own arginine. Since then, he and his team have been working to use this knowledge to create effective treatments for mesothelioma patients.

"It's great to see research into arginine starvation of cancer cells come to fruition," he said. "This discovery was driven by me from the earliest days in the lab and the new therapy ADI-PEG20 has now improved the lives of mesothelioma patients. I am grateful to all the patients and families, the investigators and their teams, and Polaris Pharmaceuticals for their commitment to defining a new cancer therapy."

Dr Tayyaba Jiwani, Scientific Engagement Manager at Cancer Research UK, said: "This study shows the power of discovery research, which allows us to delve deeper into the biology of mesothelioma and discover weak links that we can now target with ADI-PEG20. Cancer Research UK is delighted to be funding the early stages of this research, including a preliminary clinical trial that establishes the safety and effectiveness of this drug."

Studies are currently evaluating ADI-PEG20 in patients with sarcoma or glioblastoma multiforme, a type of brain tumor, as well as other arginine-dependent cancers. The success of this new type of chemotherapy in myeloma also suggests that the drug may be beneficial in treating many other types of cancer.

Mick's Mesothelioma Journey

In the 1970s, Mick worked in the boiler room of a factory and was exposed to asbestos. In 2018, he started feeling ill and lost 42 pounds, so he went to see a doctor. He became anemic and was eventually diagnosed with mesothelioma.

Mick explains: "It was a bit of a shock: I only had four months to live. His doctor referred him to Professor Szlosarek, who enrolled him in the ATOMIC-meso trial. I always believed in Peter. I said: 'I'm going to win - you can't get rid of me.' Five years later, here I am."

For two years Mick has been attending St Bartholomew's Hospital every week, accompanied by his wife Jackie or his children and grandchildren. "I will receive two injections of the new treatment - one in each arm. I haven't had any serious side effects," Mick explained. "I got to know a lot of other people who were on the trial. Over time, some of them disappeared. But I stuck with it."

Mick received compensation from his former employer for exposure to asbestos that ultimately led to mesothelioma. About 80% of mesothelioma cases are caused by exposure to asbestos in the workplace.

Two and a half years after Mick entered the ATOMIC-meso trial, the mesothelioma returned and he received a second course of treatment, this time immunotherapy. He experienced more side effects from this therapy, including encephalitis. But his cancer remains under control, and he recently celebrated his 80th birthday. Professor Szlosarek and his team plan to study why specific patients like Mick benefit so much from ADI-PEG20, hoping to discover how more people can benefit.

Mick said: "This trial has changed the lives of mesothelioma patients, allowing us to live longer. I now have five grandchildren and two great-grandchildren and I don't want to miss this."

Compiled source: ScitechDaily