̽��ֱ�� of Cambridge - brain tumours

Finding new ways to diagnose childhood brain tumours

Anonymous — Fri, 24 Mar 2023 12:48:58 +0000

Funded by ̽��ֱ��Brain Tumour Charity, this research aims to develop new ways to diagnose medulloblastoma using minimally invasive methods, protecting the quality of life of children with this diagnosis.

Medulloblastoma is the most common cancerous childhood brain tumours, accounting for 15-20% of all childhood brain tumour diagnoses. Around 52 children are diagnosed with a medulloblastoma each year in the UK. These tumours are fast growing and develop at the back of the brain in the cerebellum.

Dr Jessica Taylor, a postdoctoral researcher at the ̽��ֱ�� of Cambridge working in Professor Richard Gilbertson’s lab at the Cancer Research UK Cambridge Institute, will focus on one of the four subtypes of medulloblastoma - wingless (WNT) medulloblastoma. WNT-medulloblastoma is typically difficult to operate on, but is highly curable with chemotherapy and radiation.

̽��ֱ��research will use antibodies that have been designed to bind to the WNT-medulloblastoma cells. Once bound to the cells, they will be visible on a PET scan and can be used to diagnose this subtype of medulloblastoma. This method avoids the use of invasive surgery and so will protect children from the potential long-term, damaging effects of surgery such as memory problems and speech issues.

Dr Taylor, the recipient of a Future Leaders Award from ̽��ֱ��Brain Tumour Charity, said: “With one in four children with this tumour type suffering long-term memory loss and speech issues after surgery, it is important that we work towards improving diagnostic methods which avoid surgery.

“I hope my research will change the way medulloblastoma is clinically diagnosed and that it will improve the treatment and quality of life for children diagnosed with this disease.”

̽��ֱ��antibodies will be designed to bind to drugs that could treat WNT-medulloblastoma. This innovative approach would deliver treatments directly to the tumour, potentially replacing the need for more traditional chemotherapy. This could have several benefits including giving patients an additional treatment option and offering a more targeted therapy, potentially reducing the side effects from treatment.

Dr David Jenkinson, Chief Scientific Officer at ̽��ֱ��Brain Tumour Charity, said: “This innovative project exploits the features of WNT-medulloblastoma to create specific antibodies that will help diagnose and even treat this type of tumour, avoiding unnecessary surgery for the children diagnosed. Focusing research on non-invasive diagnostics and treatments helps to prevent long-term damage that can result from surgery.”

Adapted from a press release from ̽��ֱ��Brain Tumour Charity

Cambridge researchers are using new techniques to distinguish different types of medulloblastoma, a type of brain tumour in children.

With one in four children with this tumour type suffering long-term memory loss and speech issues after surgery, it is important that we work towards improving diagnostic methods which avoid surgery

Jessica Taylor

CRUK Cambridge Institute

Dr Jessica Taylor

Sophie Harper's story

John Huggins’ granddaughter Sophie Harper was diagnosed with medulloblastoma in 2006.

John said: “Until the age of nineteen months Sophie seemed to be a normally developing little girl, she walked at eleven months and her speech was well ahead of her age. From nineteen months she started to vomit regularly and when her mother took her to the doctors on day four, he diagnosed a virus. After ten days my daughter returned to the doctor, but again he said it was a virus. Sophie was taken to the doctor a number of times over the next two and a half months and there was no change with the doctor’s diagnosis. Sophie then started to lose her ability to walk, no longer was she the happy child she was, complaining of head pain, started falling over regularly and wanting to be carried around. It was only then the doctor agreed for Sophie to have a scan.”

Sophie’s scan took place at Norwich ̽��ֱ�� Hospital and revealed a mass on her cerebellum. She was transferred to Addenbrooke’s Hospital, Cambridge, for further tests and a medulloblastoma tumour was confirmed.

John said: “None of us had any knowledge of brain tumours and it became a huge learning curve. At that point Mum and Dad had to decide whether to take the option of curative or palliative care. Sophie always had a big personality and was such a fighter with any illness, so Mum and Dad decided they had to give her the tools to fight with and take the curative option”.

̽��ֱ��following week, Sophie underwent an operation to try and remove the tumour and the family waited anxiously in the garden of Addenbrooke’s Hospital for news. ̽��ֱ��operation was expected to last around three to four hours but Sophie was in surgery for seven and a half.

John said: “Sophie didn’t regain consciousness for thirty two days, due to the insult to her brain. She spent three months in intensive care and was now needing an oxygen supplement and having to be fed through a gastrostomy tube. Both of these would stay for the next six years of her life.

“It also became clear that there were other side effects from the operation: her speech was significantly impacted and she was unable to hold our gaze and her movements were uncoordinated and clumsy. During the time of her treatment she received more than a hundred transfusions of blood products due to low blood cell counts, but none of us can remember a single day, when she didn’t make us laugh or brighten our day. She had an amazing ability to do that.

“It is true to say, surgery had a dramatic effect on Sophie, she was no longer the child we knew before the operation.”

Just before Sophie’s eighth birthday, her family were devastated when a scan revealed another growth on her brain. She was given three months to live, but survived almost a year and sadly died shortly before her ninth birthday in 2013.

After her death, Sophie’s family set up ̽��ֱ��Sophie Elin Harper Fund with ̽��ֱ��Brain Tumour Charity to raise funds and awareness of brain tumours. Their fundraising to date totals a remarkable £38,000.

John said: “ ̽��ֱ��side effects Sophie had following surgery, with the insult to her brain, were huge and totally life changing.

“Sophie lived a very cruel life, in and out of hospital. Even the shunt fitted in her brain had to be replaced on three occasions. She never regained the ability to walk, and was always fed through a gastrostomy tube, together with an oxygen supplement, but she never complained.

“ ̽��ֱ��possibility of avoiding side effects and unnecessary surgery would be a real turning point in the treatment of medulloblastoma.”

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Scientists can detect brain tumours using a simple urine or blood plasma test

Anonymous — Fri, 23 Jul 2021 15:05:30 +0000

̽��ֱ��team say that a test for detecting glioma using urine is the first of its kind in the world.

Although the research, published in EMBO Molecular Medicine, is in its early stages and only a small number of patients were analysed, the team say their results are promising.

̽��ֱ��researchers suggest that in the future, these tests could be used by GPs to monitor patients at high risk of brain tumours, which may be more convenient than having an MRI every three months, which is the standard method.

When people have a brain tumour removed, the likelihood of it returning can be high, so they are monitored with an MRI scan every three months, which is followed by biopsy.

Blood tests for detecting different cancer types are a major focus of research for teams across the world, and there are some in use in the clinic. These tests are mainly based on finding mutated DNA, shed by tumour cells when they die, known as cell-free DNA (cfDNA).

However, detecting brain tumour cfDNA in the blood has historically been difficult because of the blood-brain-barrier, which separates blood from the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord, preventing the passage of cells and other particles, such as cfDNA.

Researchers have previously looked at detecting cfDNA in CSF, but the spinal taps needed to obtain it can be dangerous for people with brain tumours so are not appropriate for patient monitoring.

Scientists have known that cfDNA with similar mutations to the original tumour can be found in blood and other bodily fluids such as urine in very low levels, but the challenge has been developing a test sensitive enough to detect these specific mutations.

̽��ֱ��researchers, led by Dr Florent Mouliere who is based at the Rosenfeld Lab of the Cancer Research UK Cambridge Institute and at the Amsterdam UMC, and Dr Richard Mair, who is based at Cancer Research UK Cambridge Institute and the ̽��ֱ�� of Cambridge developed two approaches in parallel to overcome the challenge of detecting brain tumour cfDNA.

̽��ֱ��first approach works for patients who have previously had glioma removed and biopsied. ̽��ֱ��team designed a tumour-guided sequencing test that was able to look for the mutations found in the tumour tissue within the cfDNA in the patient’s urine, CSF, and blood plasma.

A total of eight patients who had suspected brain tumours based on MRIs were included in this part of the study. Samples were taken at their initial brain tumour biopsies, alongside CSF, blood and urine samples.

By knowing where in the DNA strand to look, the researchers found that it was possible to find mutations even in the tiny amounts of cfDNA found in the blood plasma and urine.

̽��ֱ��test was able to detect cfDNA in 7 out of 8 CSF samples, 10 out of the 12 plasma blood samples and 10 out of the 16 urine samples.

For the second approach the researchers looked for other patterns in the cfDNA that could also indicate the presence of a tumour, without having to identify the mutations.

They analysed 35 samples from glioma patients, 27 people with non-malignant brain disorders, and 26 healthy people. They used whole genome sequencing, where all the cfDNA of the tumour is analysed, not just the mutations.

They found in the blood plasma and urine samples that fragments of cfDNA, which came from patients with brain tumours were different sizes than those from patients with no tumours in CSF. They then fed this data into a machine learning algorithm which was able to successfully differentiate between the urine samples of people with and without glioma.

̽��ֱ��researchers say that while the machine learning test is cheaper and easier, and a tissue biopsy from the tumour is not needed, it is not as sensitive and is less specific than the first tumour-guided sequencing approach.

MRIs are not invasive or expensive, but they do require a trip to the hospital, and the three-month gap between checks can be a regular source of anxiety for patients.

̽��ֱ��researchers suggest that their tests could be used between MRI scans, and could ultimately be able to detect a returning brain tumour earlier.

̽��ֱ��next stage of this research will see the team comparing both tests against MRI scans in a trial with patients with brain tumours who are in remission to see if it can detect if their tumours are coming back at the same time or earlier than the MRI. If the tests prove that they can detect brain tumours earlier than an MRI, then the researchers will look at how they can adapt the tests so they could be offered in the clinic, which could be within the next ten years.

“We believe the tests we’ve developed could in the future be able to detect a returning glioma earlier and improve patient outcomes,” said Mair. “Talking to my patients, I know the three-month scan becomes a focal point for worry. If we could offer a regular blood or urine test, not only will you be picking up recurrence earlier, you can also be doing something positive for the patient’s mental health.”

Michelle Mitchell, Chief Executive of Cancer Research UK said, “While this is early research, it’s opened up the possibility that within the next decade we could be able to detect the presence of a brain tumour with a simple urine or blood test. Liquid biopsies are a huge area of research interest right now because of the opportunities they create for improved patient care and early diagnosis. It’s great to see Cancer Research UK researchers making strides in this important field.”

Sue Humphreys, from Wallsall, a brain tumour patient, said: "If these tests are found to be as accurate as the standard MRI for monitoring brain tumours, it could be life changing.

If patients can be given a regular and simple test by their GP, it may help not only detect a returning brain tumour in its earliest stages, it can also provide the quick reassurance that nothing is going on which is the main problem we all suffer from, the dreaded Scanxiety.

̽��ֱ��problem with three-monthly scans is that these procedures can get disrupted by other things going on, such as what we have seen with the Covid pandemic. As a patient, this causes worry as there is a risk that things may be missed, or delayed, and early intervention is the key to any successful treatment.”

Reference:
Florent Mouliere et al. ‘Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients.’ EMBO Molecular Medicine (2021). DOI: 10.15252/emmm.202012881

Adapted from a Cancer Research UK press release.

Researchers from the Cancer Research UK Cambridge Institute have developed two tests that can detect the presence of glioma, a type of brain tumour, in patient urine or blood plasma.

Yes

Cambridge team develops technique to ‘listen’ to a patient’s brain during tumour surgery

cjb250 — Mon, 15 Oct 2018 23:08:05 +0000

Patients with low-grade gliomas in their brains – a slow-spreading, but potentially life-threatening tumour – will usually receive surgery to have the tumour removed. But removing brain tissue can be risky as there is no boundary between the brain and tumour – the tumour infiltrates the brain. Removal of tumour can lead to removal of vital parts of the brain and resulting impairments in functions such as speech, movement and executive function (which enables the individual to plan, organise and execute tasks).

To minimise this risk, neurosurgeons open the patient’s skull and then waken them. A local anaesthetic means the patient will feel no pain, and the brain itself contains no pain receptors. ̽��ֱ��surgeon will probe the patient’s brain, applying mild electric pulses to tissue surrounding the tumour while asking them to perform a set of tasks. For example, the patient may be asked to count from one to five: if an electric pulse applied to a certain place in the brain affects their ability to perform this task, the surgeon will leave this tissue in place.

“As surgeons, we’re always trying to minimise the risk to patients and provide them with the best possible outcomes,” says Thomas Santarius, a neurosurgeon at Addenbrooke’s, Cambridge ̽��ֱ�� Hospitals. “Operating on brain tumours is always a delicate balance between removing as much diseased tissue as possible to give patients better prognosis, while minimising the risk of damage to brain functions that will have a potentially massively detrimental impact on the patient’s life.”

While the current approach is considered the ‘gold standard’, it is not perfect. It takes time to apply the pulses on different parts of the brain and it may miss out some areas that are important for certain functions. ̽��ֱ��current battery of cognitive tests that surgeons use is also limited and does not test for the essential executive function, for example.

Now, a team of scientists and clinicians from the ̽��ֱ�� of Cambridge and Addenbrooke's Hospital, led by Mr Santarius, Dr Yaara Erez and Mr Michael Hart, together with Pedro Coelho from Neurophys Ltd, has collaborated to develop a new approach that will enable patients to get a more accurate, personalised ‘read-out’ of their brain networks, and will provide surgeons with real-time feedback on the patient’s brain activity in theatre.

“At the moment, neurosurgeons only know about function in the average brain – they have no patient-specific information,” explains Dr Yaara Erez, a neuroscientist from the MRC Cognition and Brain Sciences Unit at the ̽��ֱ�� of Cambridge. “But there’s been huge progress in brain imaging and electrophysiology – our understanding of the electricity within our bodies – so why not use this information to improve brain surgery? We are aiming to bring all this knowledge into the theatre, providing surgeons with integrated data and the best tools to support their work.”

Under this approach, patients would undergo a number of neuroimaging examinations using magnetic resonance imaging (MRI) before surgery aimed at identifying not only the exact location of the tumour but also how different regions of their brains communicate with each other.

As part of this process, a 3D-printed copy of the patient’s brain will be used, showing where the tumour is located. This model is intended to help surgeons plan the surgery, discuss with the patient the potential risks from surgery and involve the patient in decisions over which tissue to remove.

“Doctors need to be able to talk through the options with patients, and we hope that using neuroimaging data and presenting this as a 3D model will help surgeons with the planning of surgery and ensure patients are better informed about the risks and benefits from surgery,” says Dr Erez.

During surgery, once the patient’s skull has been opened, the surgeon will place electrodes on the surface of the brain, to ‘listen’ to their brain activity. A computer algorithm will analyse this information as the patient performs a battery of cognitive tests, giving live feedback to the surgeon. This will enable the surgeon to predict more accurately the likely impact of removing a particular area of brain tissue.

In particular, executive function is difficult to test using electrical stimulation – in part because it involves networks of regions across the brain. Dr Erez hopes that a combination of improved cognitive tests and a more accurate understanding of an individual patient’s networks will enable surgeons to monitor potential impairment to executive function during surgery.

“This isn’t going to replace brain stimulation during surgery,” says Dr Erez, “but it will guide the surgeon and it will save time and make surgery more efficient, more accurate. It will also enable us to understand how patients’ brains adapt to the presence of a tumour and how well they recover from surgery. It involves equipment that is largely already in use in surgeries, so should be easy and cost effective to implement.”

So far, the team has obtained data from 12 patients, already providing a large amount of data to analyse, with a rich dataset from each patient, collected before, during and after surgery. Although they are currently analysing this information offline, the data will help them find the best measures to provide the required information – what the ideal tasks for patients to perform are – and then to optimise the analysis.

̽��ֱ��research has only been possible because of the interaction between researchers and clinicians from a variety of disciplines, says Dr Erez. “At Cambridge, we have different groups of neuroscientists with a range of expertise from psychology and imaging to computer science working with clinicians and surgeons at the hospital. Whatever we need, we can always find someone in Cambridge who knows how to do it!”

̽��ֱ��research is supported by the Medical Research Council, the Royal Society and ̽��ֱ��Brain Tumour Charity.

Surgeons could soon eavesdrop on a patient’s brain activity during surgery to remove their brain tumour, helping improve the accuracy of the operation and reduce the risk of impairing brain function.

There’s been huge progress in brain imaging and electrophysiology – our understanding of the electricity within our bodies – so why not use this information to improve brain surgery?

Yaara Erez

Kai Schreiber

Brains

Researcher profile: Dr Yaara Erez

Originally from Israel, Dr Yaara Erez is now a neuroscientist at the MRC Cognition and Brain Sciences Unit – a centre that not only has “a long history of great contributions to the theoretical and experimental foundations of cognitive psychology”, she says, but “is also famous for its truly lovely garden!”

Yaara’s background is in Computer Science and Psychology. She spent several years as a software developer before deciding to pursue a PhD in neuroscience, and she is now a Royal Society Dorothy Hodgkin Research Fellow. Her background is proving essential for understanding the inner workings of the brain.

“We process the information around us in an active way – we pay attention to what is relevant to us and filter out what we don’t need. We do that all the time, effortlessly and efficiently, but from a computational perspective it is a very complicated problem. We only have hints about how this is done in the brain.”

Yaara’s interest lies in the brain systems that allow us to behave flexibly, adapt our behaviour to changing circumstances, and select only the information that we need. These systems are involved in a wide range of cognitive function known as ‘executive function’, including problem-solving, keeping focus, switching focus and planning, all of which are essential to normal healthy life. “It’s important to understand these brain mechanisms because it may help us develop treatments for patients with different brain disorders that affect cognitive function, such as stroke, brain tumour, depression, and many more,” she says.

While Yaara’s research is basic science, she is interested in its clinical application and how the knowledge might be used to improve healthcare and treatments for patients. “I believe we can improve existing procedures so patients can have a high quality of life after brain surgery. We can and we should use our knowledge from basic neuroscience to improve treatments for patients.”

Her work uses a variety of techniques that involve different types of brain signals that she collects from healthy volunteers and patients with brain tumours. “This data is very complex, so requires detailed analysis, which I like. ̽��ֱ��combination of the data from the different techniques, and what we can learn from each of them, makes my work exciting and enables me to get the full picture.

Yaara recalls the day she first saw a live brain surgery on an awake patient. “As a neuroscientist, I study the brain and know quite a lot about it, but seeing a real brain and how brief pulses of electrical stimulation immediately affect behaviour was a different level of experience and truly eye-opening.”

Cambridge, says Yaara, is the perfect place for her research. “There are people from all over the world, and they all bring their expertise, knowledge, and perspective. My research is multidisciplinary in its nature, and the combination of the different expertise of people in Cambridge makes it work. We also have great facilities here and are very fortunate to have such a great ̽��ֱ�� Hospital as Addenbrooke’s as our local hospital.

“I enjoy meeting and working with people from all around the world, and the international community in Cambridge is amazing.”

Yes

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Attribution-ShareAlike

Cambridge ̽��ֱ�� and Institute of Cancer Research launch Children’s Brain Tumour Centre of Excellence

cjb250 — Thu, 22 Feb 2018 16:06:04 +0000

̽��ֱ��announcement comes as CRUK announces an investment of an extra £25 million over the next five years into brain tumour research. This is in addition to the £13 million spent each year on research and development of new treatments for the disease.

Cancer Research UK’s funding will support two new specialised centres. ̽��ֱ��first of these, the Children’s Brain Tumour Centre of Excellence, brings together world-leading experts to discover and develop new treatments to tackle brain tumours in children. A second centre focusing on adult brain tumours will open later in the year.

̽��ֱ��Centre will be led by childhood brain tumour expert Professor Richard Gilbertson, Director of the Cancer Research UK Cambridge Centre.

“By creating a hub of expertise for childhood brain tumour research in the UK, we aim to make real inroads to tackling these diseases,” said Professor Gilbertson. “Gathering this expertise together means we can shine a light on the numerous challenges and difficulties that brain tumours pose and discover new treatments to ensure that more children survive their disease.”

̽��ֱ��announcement comes as the Health and Social Care Secretary Jeremy Hunt committed an estimated £20 million in funding to tackle brain tumours and deliver a “step change” in survival rates. ̽��ֱ��funding will be invested through the National Institute for Health Research over the next five years – with the aim of doubling this once new high-quality research proposals become available.

Each year around 11,400 people in the UK are diagnosed with a brain tumour and just 14% of people survive their disease for 10 or more years.

Jeremy Hunt MP said: “While survival rates for most cancers are at record levels, the prognosis for people with brain tumours has scarcely improved in over a generation.

“Our ambition is to deliver a big uplift in the funding of brain cancer research, while galvanising the clinical and scientific communities to explore new avenues for diagnosis and treatment in the future – it is a chance to create a genuine, step change in survival rates for one of the deadliest forms of cancer.”

Sir Harpal Kumar, Cancer Research UK’s chief executive, added: “Brain tumours remain a huge challenge, with survival barely improving over the last 30 years. Since we laid out our plans to tackle this challenge in 2014, Cancer Research UK has already substantially increased its funding into brain tumours and attracted some of the world’s leading experts to the UK.

“This new funding will mean that we can accelerate these efforts further, by developing a critical mass of expertise in key areas and supporting work along the entire research pipeline to improve survival for children and adults with brain tumours.”

Cambridge leading innovative brain cancer research

Cancer Research UK (CRUK) has today announced funding for a new Children’s Brain Tumour Centre of Excellence, based at the ̽��ֱ�� of Cambridge and ̽��ֱ��Institute of Cancer Research, London.

By creating a hub of expertise for childhood brain tumour research in the UK, we aim to make real inroads to tackling these diseases

Richard Gilbertson

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Man on a mission to beat cancer

cjb250 — Mon, 14 Nov 2016 11:09:53 +0000

On the children’s ward at Newcastle General Hospital in 1986, medical student Richard Gilbertson got his first taste of life as a paediatric oncologist. He looked around the ward and saw a child in a bed, in a dark corner. “She has a medulloblastoma that has returned,” the consultant said. “What can we do for her?” asked Gilbertson, who had been fascinated by medulloblastomas – one of the commonest malignant brain tumours in children – since his first year of medicine, when he was randomly assigned to do a project on them. “Nothing,” the consultant replied. “ ̽��ֱ��only thing we can do is let her die in peace.”

“I got so angry,” remembers Gilbertson – now Professor – sitting in his airy office on the first floor of the vast glass-and-steel Cancer Research UK Cambridge Institute (CRUK CI) at the Li Ka Shing Centre. “It was the 1980s and there was nothing we could do for a child with a brain tumour. That was completely unacceptable to me. And I know it sounds contrived, but I made up my mind from that moment that I was going to do something.”

That ‘something’ was initially a number dreamed up in a Newcastle pub: relaxing with a beer after a long week, Gilbertson and his fellow medical students decided that by the time they retired, they should take personal responsibility for implementing a 15 per cent reduction in mortality, from whatever disease they chose.

Gilbertson never forgot that pledge and, 30 years later, you could argue that he’s fulfilled it. As a result of his insights into how children’s brain tumours behave, more children than ever before are surviving them. However this, he argues, is because of better patient care and understanding of the condition, not more effective treatments, earlier detection or prevention. These are the things, he says, that will fulfil his latest ambition: a world without cancer.

When Gilbertson began studying brain tumours, they were all regarded as the same disease, and needing the same treatment. He proved that the main types of tumour not only behaved differently from each other but are also totally different diseases.

“All tumours generate cells, and these cells speak different languages – express different genes – in the same way that we all speak with an accent,” he explains. “So say we had a French person, an Irish person, and a Chinese person who all spoke English, we could identify their country of origin from their accent. We thought: if we can first identify the ‘accent’ that normal cells in the brain speak with and compare them with the ‘accent’ of the tumour cells, we can trace the origin of those cells back – just like we hear a Cockney speak and we know he’s from London.”

When Gilbertson and his team studied cancer ‘accents’ in brain tumours, they fell very clearly into four different categories – four different diseases arising from four different cell types. One tumour has blood vessels like sieves, for example. It’s an achilles heel that doctors can exploit – chemotherapy drugs in the bloodstream can permeate the tumour far more efficiently.

̽��ֱ��World Health Organisation (WHO) has now adopted Gilbertson’s classification, and children around the world now receive treatment matched to their category of tumour.

All this was achieved while Gilbertson was Cancer Centre and Scientific Director at St Jude Children’s Research Hospital, Memphis, one of the world’s leading children’s cancer hospitals, where he worked for 15 years. Yet his research seemed to be taking him more and more in the direction of not just paediatric cancer but the entirety of cancer. “Of course, they are different diseases. But I firmly believe that cancer needs to be thought of as a continuum. What you’re looking at is how development goes wrong, whether you’re seven or 70.”

In 2015, Gilbertson was appointed as Li Ka Shing Chair of Oncology in Cambridge and Director of the Cambridge Cancer Centre, with access to both child and adult cancers and, he says, “the best minds in the world”. These minds – physicists, engineers, chemists – are, right now, working out how Gilbertson’s dream of a cancer-free world can become reality.

There are big ideas to be worked on. “One of the things that’s always puzzled me as a paediatric oncologist is: why don’t children get cancer more?” Gilbertson says. “After all, as children grow, they experience massive cell proliferation. Cancer happens when a cell’s DNA goes wrong. Think of them as accelerators that make cells divide too much, with no brakes. Yet paediatric cancers are quite rare – much more so than adult cancer. People say it’s because children don’t smoke or live for 70 years or do those things which cause mistakes in a cell’s DNA. I don’t buy that. I think it’s partly true. But there must be something that protects children in the design of their cells from actually getting cancer.”

Gilbertson and his team have just completed a seven-year study identifying the cells that make cancers in children and adults. When his researchers challenged healthy cells with the mutations that drive cancer, they found that children’s stem cells appeared to be intrinsically resistant.

There was something about them that stopped them making cancer – unlike the adult cells, which weren’t resistant. “That’s terribly exciting, because if I can look into a child’s cells and work out the biology that is protecting that child’s cells from cancer, then maybe we could reproduce that in an adult cell with a drug. And if you do that, you’ve got a preventative for cancer. We are working on that right now, and it’s something I will be pursuing.”

All possibilities are explored. Gilbertson’s lab is currently screening around 1.2 million compounds, found everywhere from the depths of the Amazonian rainforest to the bottom of the ocean. Out of these, four have possibilities as potential treatments and are being developed. Then there are the drugs that already exist, that have been shown to be effective against other cancers: these are being screened as well. Taking a chemical compound from a tree, crushing it up and putting it on cancerous cells is one avenue of exploration, to be sure. But making that compound into a drug that a patient can actually take is a very long process. It’s far quicker to take a drug that already exists and give it to that child with the brain tumour. “It’s a bit like when your roof is leaking and you put a saucepan on the floor,” says Gilbertson. “ ̽��ֱ��saucepan wasn’t designed to do that. It was designed to cook carrots. But it’s actually useful to catch water in.”

Innovations around early diagnosis are also being examined. Just 25 per cent of people who are diagnosed with one of the eight most common cancers in the late stages will be alive 10 years later. Diagnose the same cancers just a few months earlier, when the disease is in its early stages, and 80 per cent of those patients will be alive in 10 years. ̽��ֱ��earlier you diagnose, the better chance of a cure. And here, again, it’s all about understanding the tumour, working out its strengths and its weaknesses, finding the things it does that can be turned against it.

Gilbertson points to the work of Professor Rebecca Fitzgerald at the MRC Cancer Unit, a partner of the Cancer Centre, as a perfect example. She developed the cytosponge – the equivalent of a cervical smear for the oesophagus, a notoriously hard area in which to spot pre-cancerous changes. It’s a tiny pill containing an even tinier sponge on a ‘fishing line’. ̽��ֱ��patient swallows it, the pill hits the stomach and dissolves, leaving the sponge behind. ̽��ֱ��line is then pulled up, with the sponge scraping a cell sample from the oesophagus on the way up. “What we will see increasingly in cancer is a push towards diagnosing early, and people becoming increasingly used to going through their GPs,” he says. “If you asked my dad’s generation if they had their blood pressure checked regularly, they would say no. Those kind of early diagnostics didn’t exist then but now they do, and are common practice. I think you will see that in cancer.”

Yesterday, Gilbertson mentions, he was meeting with the inventor of a breath tester to detect lung cancer. Tumour cells have a different way of consuming food than normal cells, he explains, so they produce slightly different waste products. Some of these are volatile, and these tell-tale compounds will appear in the breath – so they can be detected. ̽��ֱ��team are also developing tests for circulating tumour DNA. It’s now known that DNA isn’t present just in cells: it floats around the bloodstream. Tumours are caused by mutations in that DNA: if you create a blood test sensitive enough to detect those mistakes, you could identify that tumour before the person even starts to show symptoms.

Imagine, he says, the conversations around cancer in the future. “If people never get cancer as we know it, they’ll be saying: ‘Oh, I’ve been diagnosed with gastric cancer but the doctor’s just fixed it.’ Imagine a world where well-person clinics test accurately for the earliest cancers every year, rather than patients walking around with tumours inside them for years on end – and only when they get ill do we do something about it. Imagine a child going into a clinic for a five-year checkup, and having a blood test which reveals she has cancer. You intervene with a relatively non-toxic treatment – even minor surgery – and that’s it.” A world without cancer, where the dark corners of the ward are banished to the history books. It’s a pledge worth pursuing.

This article is taken from CAM – the Cambridge Alumni Magazine, edition 79.

Thirty years ago, Professor Richard Gilbertson pledged to implement a 15 per cent reduction in mortality from children’s brain cancer. This is the story of what happened next.

Interview: Lucy Jolin

Carol Sachs

Professor Richard Gilbertson from the CRUK Cambridge Institute

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Brain tumours and brain injury to be focus of new Cambridge laboratories

cjb250 — Fri, 11 Nov 2016 10:07:03 +0000

̽��ֱ��John Pickard Neurosurgical Laboratories, based at Addenbrooke’s Hospital, Cambridge ̽��ֱ�� Hospitals, will contain purpose built modern laboratories and updated offices, and are named after John Pickard, Professor Emeritus of Neurosurgery. Pickard was Cambridge’s first Professor of Neurosurgery, who was in post from 1991 until his retirement in 2013. ̽��ֱ��suite consists of laboratories dedicated to neurochemistry, and imaging and treating brain tumours.

“Injuries to the brain, either through trauma or diseases such as brain tumours, can have serious lasting effects on individuals, as well as for their families and carers,” says Professor Peter Hutchinson, Head of Academic Neurosurgery at the ̽��ֱ�� of Cambridge. “Our newly refurbished laboratories will help us to better understand what is happening in response to this damage, putting us in a better position to treat the patients and improve their long-term outcomes.”

̽��ֱ��Neurochemistry Laboratory, led by Dr Keri Carpenter, aims to develop better ways of monitoring and treating brain injury by investigating how the brain responds to injury and how these responses can lead to long-term disabilities. Better treatments are needed to ensure the best outcome for each patient, and alleviate demands on carers, local authorities and NHS resources. ̽��ֱ��findings are potentially also relevant to diseases such as dementia and Parkinson’s, which often manifest at a younger age in brain injury survivors.

̽��ֱ��laboratories will be the leading unit in the UK to use microdialysis, which enables doctors to deliver molecules to and from the injured brain. This technology can be used to monitor, study and potentially treat specific areas of the brain. Researchers at the ̽��ֱ�� have pioneered the use of non-radioactive ‘labels’ administered by microdialysis to track metabolism. Microdialysis is also used to support clinical trials of drugs given intravenously to establish how effectively the drug is able to cross the ‘blood-brain barrier’, transiting from the bloodstream into the brain.

Researchers from the laboratories will work in collaboration with colleagues at the newly-refurbished Wolfson Brain Imaging Centre in the development of advanced imaging techniques, as well as with colleagues in departments such as Chemistry, Clinical Neurosciences and Medicine, and across the Cambridge Biomedical Campus.

̽��ֱ��Brain Tumour Imaging Laboratory will be the UK’s first dedicated laboratory for analysing medical imaging of patients with brain tumours. It will use advanced imaging that can be performed on clinical scanners to understand disease-related changes in and around brain tumours – including how far these tumours spread, the effect and impact this spread has on the normal brain, and how treatments such as surgery and radiotherapy affect normal brain function. ̽��ֱ��laboratory will be led by Mr Stephen Price.

̽��ֱ��Lisa Wiles Neurooncology Laboratory – named after a patient treated at Addenbrooke’s – will also be the first of its kind in the UK, and will be integrated with the operating rooms to collect and process tissue samples taken directly from cancer patients being operated on. Led by Mr Colin Watts, the team will use this new facility as a resource available to the whole of the Cambridge Cancer Centre community to support world-class research to improve our understanding of brain cancer and develop new therapies. This should enable faster, more precise diagnoses to improve the treatment of patients – including tailoring treatment to each individual patient.

“We’re very grateful to Professor Pickard and to Ms Wiles for helping us make these new laboratories a reality,” says Professor Patrick Maxwell, Regius Professor of Medicine at the ̽��ֱ�� of Cambridge. “These facilities will perform an important role in helping make a real difference to the lives of patients with brain injuries.”

Professor John Pickard was the first chairman and clinical director of the Wolfson Brain Imaging Centre, a leading biomedical imaging centre housing both MRI and PET scanners. More recently he became the first Cambridge Health Technology Co-operative Honorary Director, which is one of eight national co-operatives that receive funding from the National Institute for Health Research. ̽��ֱ��Cambridge co-operative is the only one to focus on brain injury.

A new suite of laboratories aimed at improving outcomes for patients with brain injuries and brain tumours opens today at the ̽��ֱ�� of Cambridge.

ur newly refurbished laboratories will help us to better understand what is happening in response to brain injury, putting us in a better position to treat the patients and improve their long-term outcomes

Peter Hutchinson

Roger Mommaerts

brain2 (edited)

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“Trojan horse” treatment could beat brain tumours

tdk25 — Wed, 13 Aug 2014 07:00:12 +0000

A “Trojan horse” treatment for an aggressive form of brain cancer, which involves using tiny nanoparticles of gold to kill tumour cells, has been successfully tested by scientists.

̽��ֱ��ground-breaking technique could eventually be used to treat glioblastoma multiforme, which is the most common and aggressive brain tumour in adults, and notoriously difficult to treat. Many sufferers die within a few months of diagnosis, and just six in every 100 patients with the condition are alive after five years.

̽��ֱ��research involved engineering nanostructures containing both gold and cisplatin, a conventional chemotherapy drug. These were released into tumour cells that had been taken from glioblastoma patients and grown in the lab.

Once inside, these “nanospheres” were exposed to radiotherapy. This caused the gold to release electrons which damaged the cancer cell’s DNA and its overall structure, thereby enhancing the impact of the chemotherapy drug.

̽��ֱ��process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

While further work needs to be done before the same technology can be used to treat people with glioblastoma, the results offer a highly promising foundation for future therapies. Importantly, the research was carried out on cell lines derived directly from glioblastoma patients, enabling the team to test the approach on evolving, drug-resistant tumours.

̽��ֱ��study was led by Mark Welland, Professor of Nanotechnology at the Department of Engineering and a Fellow of St John’s College, ̽��ֱ�� of Cambridge, and Dr Colin Watts, a clinician scientist and honorary consultant neurosurgeon at the Department of Clinical Neurosciences. Their work is reported in the Royal Society of Chemistry journal, Nanoscale.

“ ̽��ֱ��combined therapy that we have devised appears to be incredibly effective in the live cell culture,” Professor Welland said. “This is not a cure, but it does demonstrate what nanotechnology can achieve in fighting these aggressive cancers. By combining this strategy with cancer cell-targeting materials, we should be able to develop a therapy for glioblastoma and other challenging cancers in the future.”

To date, glioblastoma multiforme (GBM) has proven very resistant to treatments. One reason for this is that the tumour cells invade surrounding, healthy brain tissue, which makes the surgical removal of the tumour virtually impossible.

Used on their own, chemotherapy drugs can cause a dip in the rate at which the tumour spreads. In many cases, however, this is temporary, as the cell population then recovers.

“We need to be able to hit the cancer cells directly with more than one treatment at the same time” Dr Watts said. “This is important because some cancer cells are more resistant to one type of treatment than another. Nanotechnology provides the opportunity to give the cancer cells this ‘double whammy’ and open up new treatment options in the future.”

In an effort to beat tumours more comprehensively, scientists have been researching ways in which gold nanoparticles might be used in treatments for some time. Gold is a benign material which in itself poses no threat to the patient, and the size and shape of the particles can be controlled very accurately.

When exposed to radiotherapy, the particles emit a type of low energy electron, known as Auger electrons, capable of damaging the diseased cell’s DNA and other intracellular molecules. This low energy emission means that they only have an impact at short range, so they do not cause any serious damage to healthy cells that are nearby.

In the new study, the researchers first wrapped gold nanoparticles inside a positively charged polymer, polyethylenimine. This interacted with proteins on the cell surface called proteoglycans which led to the nanoparticles being ingested by the cell.

Once there, it was possible to excite it using standard radiotherapy, which many GBM patients undergo as a matter of course. This released the electrons to attack the cell DNA.

While gold nanospheres, without any accompanying drug, were found to cause significant cell damage, treatment-resistant cell populations did eventually recover several days after the radiotherapy. As a result, the researchers then engineered a second nanostructure which was suffused with cisplatin.

̽��ֱ��chemotherapeutic effect of cisplatin combined with the radiosensitizing effect of gold nanoparticles resulted in enhanced synergy enabling a more effective cellular damage. Subsequent tests revealed that the treatment had reduced the visible cell population by a factor of 100 thousand, compared with an untreated cell culture, within the space of just 20 days. No population renewal was detected.

̽��ֱ��researchers believe that similar models could eventually be used to treat other types of challenging cancers. First, however, the method itself needs to be turned into an applicable treatment for GBM patients. This process, which will be the focus of much of the group’s forthcoming research, will necessarily involve extensive trials. Further work needs to be done, too, in determining how best to deliver the treatment and in other areas, such as modifying the size and surface chemistry of the nanomedicine so that the body can accommodate it safely.

Sonali Setua, a PhD student who worked on the project, said: “It was hugely satisfying to chase such a challenging goal and to be able to target and destroy these aggressive cancer cells. This finding has enormous potential to be tested in a clinical trial in the near future and developed into a novel treatment to overcome therapeutic resistance of glioblastoma.”

Welland added that the significance of the group’s results to date was partly due to the direct collaboration between nanoscientists and clinicians. “It made a huge difference, as by working with surgeons we were able to ensure that the nanoscience was clinically relevant,” he said. “That optimises our chances of taking this beyond the lab stage, and actually having a clinical impact.”

̽��ֱ��full research paper can be found at: http://dx.doi.org/10.1039/c4nr03693j

A smart technology which involves smuggling gold nanoparticles into brain cancer cells has proven highly effective in lab-based tests.

By combining this strategy with cancer cell-targeting materials, we should be able to develop a therapy for glioblastoma and other challenging cancers in the future

Mark Welland

M Welland

A cancer cell containing the nanoparticles. ̽��ֱ��nanoparticles are coloured green, and have entered the nucleus, which is the area in blue

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Researchers develop new test for children with vision loss

sjr81 — Tue, 11 Oct 2011 15:47:27 +0000

Dr Louise Allen, a paediatric ophthalmologist at the ̽��ֱ�� of Cambridge, and Dr Adar Pelah, an electronics engineer at the ̽��ֱ�� of York, have developed a specialised visual field test system to detect peripheral vision defects, called KidzEyez.

Peripheral visual field loss in children can result from prematurity, eye disorders such as retinal dystrophy, brain conditions such as cerebral palsy, neurosurgery, drug therapy, or brain tumours.

Most children with brain tumours will develop visual field loss due to the tumour’s interference with the visual pathway, which stretches from the optic nerve at the very front of the brain to the visual cortex at the back of the brain. Unfortunately, visual field loss in young children is currently very difficult to assess; timely recognition could lead to earlier diagnosis and treatment of its cause, resulting in the prevention of severe visual impairment, improved outcomes and more individualised support.

Current techniques for measuring the peripheral visual field require the subject to sit still and maintain a steady gaze at a light target for as long as ten minutes. These tests can be difficult enough for an adult to perform, let alone a young child.

̽��ֱ��clinical need for a perimeter suitable for use in young children led Dr Allen and Dr Pelah to develop a system which is child-friendly, fast, but accurate in detecting peripheral visual field loss.

Using the KidzEyez system, the child watches a central cartoon on a video screen, while their natural looking response to a target appearing in different locations of the visual periphery is monitored remotely using a small camera located on the video screen. If the target falls within the intact visual field, the child will reflexively look at the target; if the target falls within a blind area, no response will be seen.

“KidzEyez is the first perimeter specifically designed for young children,” said Dr Allen. “Children find the testing fun and, by improving our detection and management of visual pathway tumours, KidzEyez could play a major role in preserving sight and improving our support of children with visual impairment.”

A trial of the KidzEyez perimeter at Addenbrooke’s Hospital, Cambridge has recently been completed on 74 children between three and 10 years of age, some with and some without predicted visual field loss. ̽��ֱ��results were compared with currently available confrontation testing, which involves the examination of the child’s response to a small toy held in their visual periphery. KidzEyez was found to have 100% sensitivity and specificity compared to confrontation testing but, importantly, gave an interpretable result in more than 70% of children whose concentration was too poor for confrontation testing.

Dr Allen will present the findings of the study at the conference of the British Isles Paediatric Ophthalmology and Strabismus Association this week in London.

KidzEyez has been funded by Cambridge Enterprise, the ̽��ֱ��’s commercialisation group, and the ̽��ֱ�� of York. Cambridge Enterprise is currently seeking commercial partners for licensing, collaboration and development of this technology.

Technology developed at the ̽��ֱ�� of Cambridge to detect peripheral visual field loss in young children will enable the earlier detection of brain tumours, potentially saving sight and lives.

KidzEyez is the first perimeter specifically designed for young children.

Louise Allen

Cambridge Enterprise

Dr Louise Allen

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