Professor Susan Short is fighting brain tumours with the common cold virus

Friday, 06 March 2015

Meeting of minds

Thanks to the research of Professor Susan Short, doctors could be using a common cold virus to shrink deadly brain tumours within five years. Sarah Holmes finds out how the Freemasons are supporting this groundbreaking work

There are six hundred and fifty kilometres of blood vessels in the human brain. If unravelled from London, they would stretch just short of Glasgow, yet coiled they fit into an organ just fifteen centimetres long. 

This incredible network keeps the brain’s one hundred billion or so nerve cells supplied with oxygen and nutrients. For decades, researchers have been investigating ways of using these blood vessels to administer life-saving treatments for complex diseases, including brain tumours. 

The current anti-cancer armoury relies on invasive treatments of brain surgery, chemotherapy and radiotherapy, which can cause debilitating side effects in patients. They range from hair loss and vomiting to the development of cancer in healthy tissues that have been exposed to radiation.  

By contrast, the pervasive network of blood vessels in the brain could allow doctors to send cancer-killing agents directly to the site of the tumour. It’s a targeted approach that could cut down recovery times significantly, but the treatment possibilities have remained underdeveloped as brain cancer research struggles to attract funding. 

Last year, however, new hope was instilled at the Leeds Institute of Cancer and Pathology. During a clinical trial of twelve NHS brain tumour patients, Professor Susan Short successfully delivered a commonly encountered, non-toxic virus capable of killing tumour cells, without harming healthy ones, directly to the brains of some patients. 

‘At present, the survival rates of brain cancer are not only disappointing, but the treatments themselves can also be harmful and invasive.’

Cerebral matters

It was a major breakthrough that brought the possibility of non-toxic brain cancer treatment one step closer to reality. Shortly after the clinical trial, Professor Short and her team were awarded a five-year grant worth £3 million, half of which came from The Brain Tumour Charity. Included in this was a joint contribution of £100,000 from the Masonic Samaritan Fund (MSF) and The Freemasons’ Grand Charity – a sum that enabled Professor Short to hire two more post-doctoral researchers.  

‘The research was recommended to us by distinguished cancer surgeon Charles Akle,’ says Richard Dunstan, Chairman of the Non-Masonic Grants Committee. 

‘We were fortunate enough to have him on our deciding committee and he spoke very highly of Professor Short, so that greatly boosted our confidence in her research.’

At present, the survival rates of brain cancer are not only disappointing, but the treatments themselves can also be harmful and invasive, explains Richard. 

‘If successful, this project could provide non-invasive and non-toxic forms of treatment that are an all-round safer option for brain cancer sufferers. In our view, that constitutes research of the utmost importance.’ 

For John McCrohan, Grants Director at the MSF, the fact that the project was being carried out in Leeds, away from the usual centres for funding, gave it extra significance. ‘It proves that not all high-quality research happens in London or Cambridge,’ he says. ‘We were eager to show the masonic community that our funding could be helping research happening right on their doorsteps.’

‘In Professor Short’s research, a harmless household pathogen is used, producing mild, flu-like symptoms at worst.’

The funding gap

It’s not the first time the Grand Charity and the MSF have combined to support a medical research cause, with previous contributions benefiting work with both prostate and ovarian cancer. This latest award, however, will help to find desperately needed treatments for a cancer that has been nationally overlooked for the past decade.

Between 2002 and 2012, brain cancer research received just £35 million in National Cancer Research Institute funding compared to the £351.5 million spent researching cures for breast cancer. As a result, survival rates have not changed much in the past forty years.

In fact, recorded cases of brain cancer have increased since the 1970s, rising twenty-three per cent for men and twenty-five per cent for women. Despite accounting for just one per cent of cancer diagnoses, brain tumours are responsible for three per cent of all cancer deaths each year. Such damning odds have driven development of The Brain Tumour Charity’s latest research strategy, A Cure Can’t Wait, which aims to secure at least £20 million of investment over the next five years. The hope is to attract more people like Professor Short into the field. 

‘I worked with patients suffering from brain tumours very early on in my career,’ says Professor Short. ‘I enjoyed it, but it was very obvious that more research was needed to improve the outcomes of their treatments. So when I started my PhD, I decided to apply the work to glioma.’

Glioma is a primary form of brain tumour made up of cells resembling the supportive glial cells in the brain and spine, and the focus of Professor Short’s latest research. 

It is one of the most aggressive and fastest-growing tumour types, with patients usually surviving for between twelve and eighteen months after diagnosis, depending on how advanced the tumour has become.

Over the next five years, Professor Short’s work will look at how harmless viruses can be used to help attack and diminish these primary tumours, as well as secondary metastatic varieties. Called oncolytic viruses, these parasitic agents can preferentially infect and kill cancer cells.

‘The aim is to develop a non-toxic form of treatment that can be used in conjunction with the traditional methods to increase the number of tumour cells that we kill,’ says Professor Short. ‘In theory, the viruses would be injected into the patient intravenously before being carried through their bloodstream to the brain where they could act on the tumour cells.’ 

The success of this theory has already been proved in the earlier clinical trial, and it’s an outstanding feat given the numerous biological obstacles that have developed to protect the brain from foreign agents – even if they are cancer-killing viruses.

The most complicated is the blood brain barrier, a unique protection system that prevents harmful pathogens from infiltrating the brain’s bloodstream. 

The second is the body’s own immune response against the virus while it is in circulation.   

‘We believe that at least some of the virus is carried intracellularly through the bloodstream and released only at the tumour site,’ explains Professor Short. ‘The immune cells, which are derived from bone marrow, protect the virus from antibody attack so that it can’t be neutralised before it reaches the brain.’

Professor Short theorises that once in the brain, the virus invades the tumour cells, causing them to explode and die. ‘There are two ways that the virus could act on the tumour cells,’ she explains. ‘Firstly it could be a direct toxic effect of the virus, which stops the tumour cells from being able to divide and grow so they die. The second is that the virus triggers a response from the local immune cells. This would encourage the immune cells to break down the tumour cell along with the virus.’

Known as immunotherapy, this form of cancer treatment is particularly advantageous for brain cancer sufferers because it lacks the painful side effects of conventional treatment. In Professor Short’s research, a harmless household pathogen called reovirus is used, producing at worst mild, flu-like symptoms in the patients. 

Ultimately, Professor Short hopes that the treatment will be available for all brain cancer patients through mainstream healthcare, although she estimates that this would be unlikely to happen for another two to three years. First, she aims to improve her understanding of how the virus attacks the tumour cells, before opening it up to more patients through clinical trials. 

Alongside this main tranche of research, Professor Short’s team will also be investigating ways to stop tumour stem cells from reseeding after radiotherapy, as well as improving their understanding of the cell-based delivery system of the virus. It’s early stages yet, and although the team can’t confidently calculate the impact the research will have on patient survival rates, Professor Short remains optimistic.

‘One of the nice things about this study is that it’s a completely new treatment option,’ she says. ‘So many other approaches to treating tumours haven’t worked, but this gives patients hope. It’s another positive step towards overcoming brain cancer.’ 

The case for research

Tim Clarke

Tim, forty, was diagnosed with a grade IV brain tumour in February 2011. The prognosis was not good, and he was told he probably wouldn’t survive beyond eighteen months. 

Even so, he went through the usual treatment process. Four years later, Tim is still here. ‘Nobody knows why I’m still around, and in a sense that makes it harder,’ he says. ‘There’s such a lack of understanding about the disease; even the treatments all seem a bit random. There’s no guarantee they will work. I have friends who were diagnosed and died within a year. Nobody can tell what’s going to happen, and that is what’s most frustrating.’

Tim hopes that with more essential research, brain cancer patients can someday be given the same odds of survival as other cancers. ‘When you don’t understand what’s happening inside your mind, it’s impossible to go forward. That’s where the research comes in.’

Cariss Evans

As a nurse, Cariss, twenty-nine, knew something wasn’t right when she kept suffering from bouts of intense déjà vu. ‘I could be driving the car, and all of a sudden my face would prickle with heat and this horrible feeling of panic would strike me,’ she recalls. 

It turned out to be a grade III oligoastrocytoma growing behind her eye. Cariss was devastated. In June 2014, she had brain surgery to remove as much of the tumour as possible, before undergoing intensive rounds of radiotherapy and chemotherapy over the course of the rest of the year. ‘The treatment made me feel even worse than the tumour itself,’ she says. ‘It was such a gruelling process.’

The lack of understanding about what caused this disease was equally disheartening. ‘In the news, they put it down to bad luck, but there’s got to be a reason. That’s why research is so vital, so we can find out what causes brain cancer and treat it effectively.’

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