Arginine Starvation Abates Rare Lung Cancer

A Phase 3 clinical trial, led by Peter Szlosarek, MD, PhD, professor at Queen Mary University London, has unveiled a breakthrough in the treatment of malignant pleural mesothelioma (MPM), a rare and often rapidly fatal form of cancer with limited therapeutic options.  

The ATOMIC-Meso trial, a randomized placebo-controlled study of 249 patients with MPM, found that a treatment—that combines a new drug, ADI-PEG20, with traditional chemotherapy—increased the median survival of participants by 1.6 months, and quadrupled the survival at 36 months, compared to placebo-chemotherapy.  

The findings are significant, as MPM has one of the lowest five-year survival rates (around 5–10 percent) of any solid cancer. This innovative approach marks the first successful combination of chemotherapy with a targeted anticancer drug developed for this disease in 20 years. 

What happens in malignant pleural mesothelioma? 

MPM is a rare, aggressive cancer that affects the lining of the lungs and is associated with asbestos exposure. It’s usually treated with potent chemotherapy drugs, but these are seldom able to halt the progression of the disease.  

The premise behind this new drug treatment is elegant in its simplicity—starving the tumor by cutting off its food supply. All cells need nutrients to grow and multiply, including amino acids like arginine. ADI-PEG20 works by depleting arginine levels in the bloodstream. For tumor cells that can't manufacture their arginine due to a missing enzyme: Their growth is thwarted.  

The ATOMIC-meso trial is the culmination of 20 years of research at Queen Mary’s Barts Cancer Institute that began with Szlosarek’s discovery that malignant mesothelioma cells lack a protein called ASS1, which enables cells to manufacture their own arginine. He and his team have since dedicated their efforts to using this knowledge to create an effective treatment for patients with MPM. 

Szlosarek said,  “It's truly wonderful to see the research into the arginine starvation of cancer cells come to fruition. This discovery is something I have been driving from its earliest stages in the lab, with a new treatment, ADI-PEG20, now improving patient lives affected by mesothelioma.” 

There are ongoing studies assessing ADI-PEG20 in patients who have sarcoma or glioblastoma multiforme and other cancers dependent on arginine. The success of this novel chemotherapy in MPM also suggests that the drug may benefit the treatment of multiple other types of cancer.  

- This press release was originally published on the Queen Mary University of London website