A breakthrough in treatment for an aggressive fatal lung disease has been made thanks to a two decades’ old discovery by a University of Leicester cancer specialist.
Professor Dean Fennell, who is Chair of Thoracic Medical Oncology at Leicester, was a junior doctor at St. Bartholomew’s Hospital, London in the early 2000s when he and colleague Professor Peter Szlosarek hit upon a novel way to fight malignant mesothelioma (MPM).
Their study, written when Professor Fennell had moved to Belfast, proposed a method of starving mesothelioma cancer tumours, by cutting off their food supply.
Now, almost 20 years later, a breakthrough clinical trial has taken place, which has seen patients in Leicester given a new combination chemotherapy treatment, inspired by the study.
Results from the trial, led by Queen Mary University of London, have shown the treatment significantly increases the survival of people with MPM, a rare but rapidly fatal type of cancer with few effective treatment options.
The phase three clinical trial, was led by Professor Szlosarek at Queen Mary and sponsored by Polaris Pharmaceuticals.
“It’s incredibly gratifying to see our collaboration all of those years ago to finally be put into practice – it’s been something of a lifetime’s work for us both,” said Professor Fennell.
“The trials represent a successful bench-to-bedside collaboration in which the strategy published years ago has now been proven to work in patients in a pivotal clinical trial, when added to chemotherapy.
Being based in Leicester, it’s been personally pleasing that patients from the city were able to benefit from this new treatment, which is targeted to the most aggressive form of mesothelioma.”
The ATOMIC-meso trial, a randomised placebo-controlled study of 249 patients with MPM, found that a treatment – which 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 of any solid cancer, of around five-to-10 per cent. This innovative approach marks the first successful new type of chemotherapy developed for this disease in 15 years.
MPM affects the lining of the lungs and is associated with exposure to asbestos. 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 tumour 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 tumour cells that can’t manufacture their arginine due to a missing enzyme, this means their growth is thwarted.
The ATOMIC-meso trial is the culmination of 20 years of research at the Barts Cancer Institute that began with Professor Szlosarek’s and Professor Fennell’s discovery that malignant mesothelioma cells lack a protein called ASS1, which enables cells to manufacture their own arginine. Professor Szlosarek and his team have since dedicated their efforts to using this knowledge to create an effective treatment for patients with MPM.
Professor Szlosarek said: “My collaboration with Dean when we first met as junior doctors at Bart’s to swap a weekend on call in 2005 highlights the role of serendipity in fostering research. Generosity of spirit is what drives true innovation for the benefit of patients.”
