Brain tumour's 'addiction' to common amino acid could be its weakness

Starving a childhood brain tumour of the amino acid glutamine could improve the effect of chemotherapy, according to an early study led by Queen Mary University of London (QMUL) and funded by Children with Cancer UK and the Medical Research Council.

Medulloblastoma is the most common solid primary brain tumour in children and a major cause of mortality in childhood cancers. Current treatments include a combination of surgery, radiotherapy and chemotherapy, and are effective in a majority of cases, but often associated with significant side effects, such as mental and physical disabilities.

First author Maria Niklison-Chirou from QMUL said: "If we can confirm in human patients that a glutamine restriction diet can be tolerated and is effective, it may be possible to use it to reduce the drug doses required to treat a proportion of patients with medulloblastoma. This may lead to more patients being cured or allow survivors to have a better quality of life."

Cliff O'Gorman, Chief Executive of Children with Cancer UK, which co-funded the study, said: "We welcome these findings, which open up the possibility of kinder, more effective precision treatment for young patients with medullobastoma. Children and young people with this devastating condition face aggressive treatments that can have a long-term impact on their health and well-being. It is crucial that we build on encouraging findings like these by investing in further studies and clinical trials to make cutting-edge treatment a reality for young cancer patients in the UK."

Dr Mariana Delfino-Machin, MRC Programme Manager for cancer, said: "Medulloblastoma is the most common type of aggressive brain tumour in children, and the MRC is therefore proud to support research into this dreadful disease, including studies that aim to understand the molecular mechanisms that support the growth of such tumours. Studies of this nature are crucial, early steps in the process of developing more effective treatments that may also reduce the side-effects caused by standard therapies."

The study, published in Genes & Development, looked at cells from medulloblastoma patients, and mice which had the disease. The researchers studied the metabolic processes that allow the tumour cells to grow, including the absorption of amino acids, with the aim of identifying new approaches to inhibit their growth and enhance current treatments.

The team found that a proportion of medulloblastoma were 'addicted' to glutamine - an amino acid which is usually non-essential in normal cells.

They then fed a glutamine-restricted diet to mice with the disease, and found that this enhanced the effect of chemotherapy, and increased the life span of mice, even when they were treated with lower doses of chemotherapy.

The researchers warn that although these preclinical results are promising, further studies are required to assess whether a similar approach can be applied to human patients.

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Research paper: 'TAp73 is a marker of glutamine addiction in medulloblastoma'. Niklison-Chirou et al. Genes & Development. doi: 10.1101/gad.302349.117. Available here: http://genesdev.cshlp.org/content/early/2017/09/26/gad.302349.117.abstract

Children with Cancer UK is the leading national children's charity dedicated to research into cancer in children and young people. Inaugurated in 1988 by Diana, Princess of Wales, in memory of Jean and Paul O'Gorman our aim is to improve survival rates and quality of survival in young cancer patients and to help research ways of reducing cancer incidence. Every year we invest more than £4 million in new research across the full range of childhood cancers. We currently have more than 60 projects under way at leading centres around the UK.

Queen Mary University of London (QMUL) is one of the UK's leading universities with 23,120 students representing more than 160 nationalities.

A member of the Russell Group, we work across the humanities and social sciences, medicine and dentistry, and science and engineering, with inspirational teaching directly informed by our research. In the most recent national assessment of the quality of research, we were placed ninth in the UK amongst multi-faculty universities (Research Excellence Framework 2014).

As well as our main site at Mile End - which is home to one of the largest self-contained residential campuses in London - we have campuses at Whitechapel, Charterhouse Square, and West Smithfield dedicated to the study of medicine and dentistry, and a base for legal studies at Lincoln's Inn Fields.

Queen Mary began life as the People's Palace, a Victorian philanthropic project designed to bring culture, recreation and education to the people of the East End. We also have roots in Westfield College, one of the first colleges to provide higher education to women; St Bartholomew's Hospital, one of the first public hospitals in Europe; and The London, one of England's first medical schools.

Today, as well as retaining these close connections to our local community, we are known for our international collaborations in both teaching and research.

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Thirty-two MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.mrc.ac.uk