Scientists researching one of Britain's deadliest rare cancers, mesothelioma, at Queen Mary's Barts Cancer Institute studied how cancer cells are not able to survive and continue growing when starved of the amino acid 'arginine'. Cells are normally able to make arginine themselves, but research found around half of tumours lacked this ability and need to be fed arginine in order to survive, leaving it vulnerable to starvation.
The identification of this 'Achilles' heel' led to a clinical trial led by Queen Mary (sponsored by Barts Health NHS Trust and funded by Cancer Research UK) to test a new drug that targets this weakness.
68 patients took part in the trial and results so far have been extremely promising. Treatment with the arginine lowering drug significantly slowed down disease progression amongst 44 patients receiving the drug and best supportive care*, extending progression-free survival by almost 6 weeks (compared with the 24 patients receiving best supportive care alone).
The drug, ADI-PEG20**, deprives the tumours of their external source of arginine (which comes from blood, via the food we digest). The tumour cells then die because they don't have this essential nutrient to make proteins and various other chemicals needed by tumours.
These findings could pave the way for a new approach to slowing the progression of mesothelioma. This is the first time a targeted drug treatment has been designed for this type of cancer with a positive effect in a randomised study of patients with mesothelioma.
Mesothelioma is a cancer affecting the 'protective wrapping' around our organs, particularly the tissue surrounding the lungs. It has become steadily more common since the 1960s due to asbestos exposure and the UK now has the highest rate of mesothelioma deaths in the world. Around 1 in 10 carpenters over the age of 65 can expect to develop the disease.
Dr Peter Szlosarek, Clinical Senior Lecturer at Queen Mary University of London (Barts and The London School of Medicine and Dentistry), comments:
"Mesothelioma is one of the UK's deadliest cancers with rates increasing almost four-fold since the early 1980s***. Despite this, it remains relatively under the radar and there is very little research on how to treat this form of cancer with new therapeutics. Our research found that putting the tumours on an arginine starvation diet was an effective way of weakening the cancer, which in turn prolonged progression-free survival amongst patients. Our latest research suggests that combining arginine starvation drugs with standard chemotherapy could show an even stronger effect in combatting mesothelioma. With the positive signal coming from the current trial, we are eager to launch this new combination trial in early 2014"
Why is this drug promising?
- A key issue with cancer drugs is their tendency to be quite toxic, due to the fact they affect healthy cells as well as tumour cells.
- The new drug used in this trial, ADI-PEG20, only affects the necessary tumour cells and seems to lack serious side effects.
Why is this form of cancer important?
- Last year approximately 2500 people in the UK were diagnosed with mesothelioma and patient survival is typically only up to one year from diagnosis.
- The UK is disproportionately affected by mesothelioma, accounting for more deaths than any other country in the world. (To put it in perspective, last year there were only 3500 new cases of mesothelioma in the whole of the USA, whose population is five times the size of ours).
- While still relatively rare, mesothelioma deserves our attention as the number of cases is rising steadily by around 100 cases each year. (By comparison there are less than 1,000 deaths due to cervical cancer per year).
- We need better treatments for this disease; no significant advance has been made in the last 10 years since a standard for chemotherapy was set in 2003 and surgical options are limited.