British Science Week 2018: how our pioneers are exploring cancer

If we’re going to take cancer down then we’re going to need new and innovative ideas. In 2015, we launched our Pioneer Award, a funding scheme that allowed any researcher, no matter what their background or track record, to pitch their idea to a committee with a whole range of science and tech expertise. If the idea seemed scientifically sound they could get up to £200,000 over two years to test it out.

The response has been amazing. So in the spirit of British Science Week, we caught up with some of our Pioneer Award winners to see where they’re projects have taken them, if they’ve discovered anything surprising and any challenges that have cropped up along the way.

Dr Stephen Royle

Dr Stephen Royle is studying how cells replicate and divide. This process goes wrong in cancer and he won a Pioneer Award in 2017 to work out how the disease starts when packages of DNA split incorrectly.

Chromosomes mismatching within a cell. Cristina Gutiérrez Caballero

Cells divide for normal growth and repair, and to do this they double then split their DNA – their genetic blueprint. DNA is packaged into structures called chromosomes, and sometimes these chromosomes don’t get shared properly when a cell divides, which can lead to cancer. Cells have got ways to check that this doesn’t happen, but these can fail. We wanted to find out why they fail and what happens to the chromosomes that don’t get shared properly.

So far, we’ve developed a system where chromosome sharing frequently goes wrong in cells. But we faced the unexpected challenge that most cells we use in the lab really don’t like to do this. They would rather die or fail cell division than to make a mistake in chromosome sharing – this tells us it’s a very important process. We know that these mistakes are more common in cancer and so we’re finding out why.

The film shows a cancer cell undergoing a stage of cell division called mitosis. It makes a mistake sharing the DNA between the two daughter cells, meaning that one daughter cell ends up with extra bundles of DNA called micronuclei (marked with arrows). These micronuclei are vulnerable to cancer-causing DNA damage. How micronuclei form is mysterious and this is what we are working to solve during this award. Our approach will let us track what happens to these cells as they go on to divide again, hopefully suggesting ways to stop or reverse the problems.

If DNA packages split incorrectly when a cell divides, it can lead to cancer. We gave Dr Stephen Royle (@clathrin) a Pioneer Award to work out how this happens: https://t.co/cgNc98H5hr #BSW18 pic.twitter.com/ovGO6guSi1

— Cancer Research UK (@CR_UK) March 18, 2018

Professor Eleanor Stride

Transmission Electron Microscope image of tiny oxygen bubbles. Image credit: Josh Owen, Oxford University.

Tumours often become short oxygen as they grow, which can make cancer harder to treat. A multi-disciplinary team led by Professor Eleanor Stride won Pioneer Award funding in 2016 to develop a drink containing tiny bubbles of oxygen, which could help to get oxygen back into tumours and boost the effectiveness of cancer treatments.

I’ve been working throughout my career to improve the delivery of drugs using bubbles. My pioneer project has the same drive, but using a completely different approach.

The inspiration for this project came from a phone call, strangely enough. I had been interviewed for a BBC documentary on my work to use microbubbles to improve cancer treatment, and that’s when I got a call from my collaborator Ray Averre of Avrox Technologies to ask if it would be possible to make a sports drink using tiny bubbles of oxygen.

I didn’t think a drink was the best way to deliver oxygen bubbles into the bloodstream at first. But then I found some old research papers from the former Soviet Union that suggested it might be possible. They were doing it in a fairly gruesome way, by pumping oxygenated egg white foam (essentially raw meringue) into people’s stomach. But it did seem to have some effect so, we thought let’s see if we can adapt our microbubble technology to make a drink. And to everyone’s astonishment, it worked!

Once we knew we could do it, there were obvious potential applications for cancer treatment. That was around the same time the Pioneer Awards were launched and they were looking for ‘out-there’ ideas, so we applied. And so far, it’s been extremely exciting.

Since we got the award we’ve shown that it is possible to get oxygen bubbles to travel from the stomach to a tumour in mice, and now we’re working on understanding how it works together with Professor Katherine Vallis in Oxford. We’re also investigating if the bubble drink boosts treatment response in a similar way to when we inject oxygen microbubbles with Professor John Callan and Professor Anthony McHale at Ulster University.

Our biggest challenge has been getting permission to do some of these experiments, because they seem so weird! Even though the drink is extremely safe, and much more pleasant for patients than having a drip, it’s all brand new for the ethics committee. So we’ve had to answer a lot of questions.

We’ve also had to create our own techniques as we go, because there isn’t a single instrument that can measure the amount of oxygen trapped in bubbles in a sample.

Finally, we’re looking at other applications for the drink, and we’re planning to take this forward on multiple fronts.

Dr Paul Brennan

Glioblastoma is an aggressive brain tumour that’s very hard to treat.

Dr Paul Brennan is a brain surgeon who studies brain tumours at the University of Edinburgh. He won a Pioneer Award to see if he could use metal implants to target chemotherapy directly to the brain and kill an aggressive type of brain tumour called glioblastoma. 

The big thing with this project was trying to find a way to reduce the side effects of drugs that we know work against glioblastoma, and at the same time take advantage of surgery. Even if you get most of the brain tumour out it comes back again, so we were wondering if you could leave something in the brain cavity that would help target chemotherapy precisely to the tumour to destroy the remaining tumour cells responsible for the disease coming back. People have experimented with this idea before but they used biological materials that didn’t specifically target the tumour, which could therefore harm healthy brain tissue. Instead we’re using a metal called palladium that can activate a chemotherapy drug very precisely in the brain.

I think the lightbulb moment struck me when I was reading a thesis on palladium from my colleague’s PhD student. They had a smart way to use palladium in drug delivery, and I thought this was crying out to be tried in brain tumours. That’s when I knew we needed to try putting palladium in the head.

Brain tumour cells in a dish with palladium beads. Image credit: Dr Paul Brennan.

Since getting our award in 2016, we’ve altered the chemical structures in some glioblastoma drugs to make them safer than they used to be. For example, we’re working on a drug used for bowel cancer that was once thought to be too toxic for the brain called irinotecan (Campto). As well as developing new drugs to work with the palladium catalyst, we also made a discovery that changed the way we work and think in drug discovery – some of the presumptions people make about drug screening for glioblastoma could be wrong. We realised this whilst making a certain glioblastoma drug less toxic so it could be used with the pallidum implant. When we tested our new compound alongside the original drug, we found that the cell lines used by scientists for glioblastoma research did not die with either drug. But we know from the clinic that it can kill brain tumour cells. After some investigation we realised that the drug was invented before these commonly used cell lines, and so were never put through these tests. This means that other drugs that have previously been discarded because they haven’t destroyed these modern cell lines might actually work.

A metal called palladium might help treat brain tumours. We spoke to Dr Paul Brennan who’s testing out this new treatment idea #BSW18 #BrainWeek https://t.co/cgNc98H5hr pic.twitter.com/qEB2jJUC2b

— Cancer Research UK (@CR_UK) March 14, 2018

Dr Kalnisha Naidoo

A microscope image showing a lymph node. Image credit: Dr Kalnisha Naidoo

Dr Kalnisha Naidoo won Pioneer Award funding in 2016 to develop a new ‘living’ technique that could help scientists study breast cancer that’s spread to the lymph nodes in the armpit.

My ‘light bulb’ moment happened years ago, when I was doing my PhD. I was trying to understand how pancreatic cancer spreads (metastasises) to lymph nodes, using human cells and mice to model the process in the lab.

My housemate at the time was training to be a clinical perfusionist, who operate the heart-lung bypasses during heart surgery at the hospital. We were chatting about our work and I suddenly thought: ‘Why not use that technology to create a living, human model of cancer spread?’ It would allow us to build a more complete and relevant picture of what’s happening to cancer in the body.

I held onto the idea for a while, until I gained more experience. In my current post, I’m lucky enough to be surrounded by a progressive team of people who were willing to support me when I applied for the Pioneer award.

People have kept other organs, like lungs and kidneys, alive using this technique (perfusion), mainly in the transplantation field. But human lymph nodes have never been modelled in this way.

Our research is only possible because of the help of women with breast cancer, who are having lymph nodes removed as part of their treatment. With their permission, we’ve collected some of the lymph nodes that have been removed and, so far, we’ve managed to keep them alive for 12 hours. This is as long as has been done in transplant organs as far as we know, so we’re excited. The aim is to get to five days.

Right now, we’re still checking to see that the model is working – but so far the data is encouraging. If we succeed there is so much potential with this system. We hope to use it to test drugs and to image the different cells that are in the lymph nodes, to name a few.

I’m very interested in figuring out precisely how metastasis happens so that we can try to stop it. I also want to understand how the immune system might react to cancer and how it can stop or facilitate the spread. These lymph nodes give us an opportunity to approach these questions in a different way.

This project has reminded me of just how important it is to push the boundaries of how we use human tissue, because it’s worth it. We should always strive to find new ways to think about things, even though it may take us out of our comfort zone.

This award has really opened up possibilities, and I’m incredibly grateful for it.

Dr Sarah Bohndiek

An image taken by the special camera that our physicists in Cambridge are developing. Image credit: Calum Williams & Sarah Bohndiek.

Dr Sarah Bohndiek, a physicist from the University of Cambridge, received a Pioneer Award with her colleague Dr George Gordon in 2017. They’re hoping to use the full rainbow of light to detect the changes in cells lining the oesophagus that might develop into cancer.

Normal cameras can’t detect all the different colours in light or the angles that it travels at. But our new camera can. We know that when cancer cells start to develop they absorb and reflect light differently to healthy cells, so this camera might be able to detect these early changes.

So far, we’ve created a prototype of one of these cameras and we’ve already got some imaging data. At the moment we’re taking pictures of a Rubix cube, but next year we’re hoping to stick it onto an endoscope to see if it can be used to photograph the throat and capture changing cells in the oesophagus.

The biggest challenge we’ve faced so far is trying to get our special filter on commercial cameras. It’s really tricky, we’ve broken a lot along the way. At the moment we’re using Raspberry Pi cameras, which are actually children’s cameras, because they’re only £20 a pop! If we manage to get the camera to work on an endoscope then we’re thinking of trying to develop it further so it can be used in robotic surgery.

It’s #BSW18! 🔬📊 All week we’ll be catching up with our pioneering scientists who’ve been given up to £200,000 to pursue an innovative, high-risk idea that could change the way we tackle cancer. First up is physicist Dr Sarah Bohndiek: https://t.co/cgNc98H5hr pic.twitter.com/9x7TSAPhOr

— Cancer Research UK (@CR_UK) March 9, 2018