Tackling brain tumours, understanding immunotherapy and revealing cancer’s genetics at the end of life – accelerating progress at our Centres

Up and down the country, our Centres are leading the way in research and trials that are changing how patients are treated and cared for.

Each Centre links hospitals to universities and research institutes, allowing the science to be matched with the clinical need. And ensuring patients get pioneering new treatments quickly.

Some Centres also have specialist skills, linked to certain types of cancer or different treatments. So, to nurture these skills and help share them with other Centres, we are giving their expertise a financial boost with four new UK-wide Centres’ Network Accelerator Awards.

Each lead Centre will get a pot of up to £4.4 million over five years to partner with other Centres and build up the resources, skills and infrastructure needed to speed up research, particularly for cancers where survival is still poor.

And with aims that range from uncovering the secrets of what fuels brain tumours to boosting the power of immunotherapy, the four latest projects we’re supporting – as we’ll explore below – make for inspiring reading.

Understanding the evolution and final stages of cancer

Over the last few years one of the biggest leaps we’ve made in our understanding of cancer is revealing its sheer complexity. Cancers are genetically diverse and can twist and turn over time, evolving to survive treatment and carry on growing.

But there’s one area scientists still know little about. What’s happening in tumours towards the end of life?

Dr Mariam Jamal-Hanjani, a clinician in Professor Charlie Swanton’s lab at University College London, is working on a study to collect tumour samples, after death, to help scientists understand very advanced cancer better.

She tells us about the PEACE study, which will use the Centre Network Accelerator Award to help roll the study out nationally.

We will have genetic information tracking cancer from diagnosis, throughout the disease, and now to the point of death. It’s the entire cancer journey, the ultimate evolution of cancer from beginning to end

– Dr Mariam Jamal-Hanjani

“It was about three years ago – a cold, grey November day – that Charlie mentioned to me, ‘You know, we should set up a post-mortem study’. To be honest, I wasn’t certain patients would want such thing.”

Most people associate the phrase ‘post-mortem’ with an autopsy – an examination carried out to establish the cause of death. But the phrase literally means ‘after death’. And in the case of the PEACE study, the researchers are collecting samples from consenting patients just after death to unravel what happens in those final stages of cancer.

“We collect samples of tumours from the original site where it began and the organs it spread to, and take blood samples to analyse cancer cells and DNA circulating in the bloodstream. We need to collect the samples fairly soon after death, so there is a huge team of people involved,” explains Jamal-Hanjani.

“It’s going to be a really powerful study when combined with clinical research like the Cancer Research UK-funded TRACERx study,” says Jamal-Hanjani. “We will have genetic information tracking cancer from diagnosis, throughout the disease, and now to the point of death. It’s the entire cancer journey, the ultimate evolution of cancer from beginning to end.”

Patients with terminal cancer are asked if they’d like to take part while they are well enough to understand the study and give informed consent, and doctors and nurses try to involve relatives in the decision as much as possible too. While they were setting up the PEACE study, Jamal-Hanjani tells us that it was actually the patients who were the most adamant that the study should go ahead.

“At the time we had the idea of setting up the study, there were very few opportunities for patients to leave their bodies to further cancer research – which is still the case today. And it’s something some patients desperately wanted to do.”

The PEACE study opened last year, and Jamal-Hanjani noticed that interest grew rapidly among doctors and patients alike. “We had to turn patients away because we didn’t have enough money to include everyone,” she explains. “It was heart-breaking.”

The study will be particularly valuable for getting information about tumours that doctors can’t take a biopsy from while the patient is alive, like some brain tumours.

The roll-out of this study will give patients a choice to contribute to research after their death. Understanding the final stages of cancer could be a step towards improving treatments for advanced disease.

Understanding immunotherapy’s potential

Immunotherapy has been filling the science headlines lately. On the surface it sounds simple – capture the might of the immune system and turn it against cancer.

But decades of research has shown that turning the immune system on tumours certainly isn’t easy. And there’s still plenty that scientists don’t know. For example, only around half of patients with advanced skin cancer that are treated with drugs designed to release the immune system’s ‘brakes’ will see their tumours respond.

And according to Professor Tim Elliott, from the University of Southampton, the researcher heading up the second Centre project, we don’t yet know why this is.

We hope to be able to come up with ways to predict how likely any given immunotherapy is to help a patient

– Professor Tim Elliott

“Immunotherapies can also cause some fairly serious side effects,” he explains. “And while we’re getting better at managing these, we still don’t want to be giving patients these treatments if they are not going to benefit.”

To tackle this, Elliott and his team will be taking immune cells from inside tumours and collecting every last detail about them – exactly what types of immune cells are there and what genes are turned on and off in the different groups of cells.

“We’re going to start by looking at samples from patients with oesophageal, skin and lung cancer who are taking part in clinical trials,” Elliott tells us. “By comparing how well different immunotherapies worked with the detailed samples we’re taking, we hope to be able to come up with ways to predict how likely any given immunotherapy is to help a patient.

“But more than that,” he adds, “we’re also hoping to find ways of better tailoring immunotherapy to individual patients, finding more effective combinations with other treatments, and of course looking to reduce side effects.”

And, according to Elliott, Southampton is ideally placed to coordinate this work.

“Southampton is a really strong hub for immunotherapy, and we have the right people and the right environment to turn promising lab experiments into treatments in the clinic.”

Getting the best from new radiotherapy technologies

There are a lot of exciting new radiotherapy techniques out there. Stereotactic ablative radiotherapy (SABR for short), magnetic-resonance image (MRI) guided radiotherapy, and proton beam radiotherapy all kill cancer cells using radiation – much like standard radiotherapy – but advances mean they are more precise.

SABR achieves this precision by targeting the tumour with radiation beams from multiple angles. MRI-guided radiotherapy allows radiotherapy specialists to see a 3D map of a tumour during treatment, adjusting treatment accordingly. And proton beams stop once they’ve reached their target, shielding tissue around the tumour from potentially damaging radiation.

We’d like to see radiotherapy becoming more targeted so we can give bigger doses in fewer treatments

– Professor Kevin Harrington

But in many cases it’s not clear which type of radiotherapy works best for each patient. So the third project, led by Professor Kevin Harrington at The Institute of Cancer Research in London, will attempt to find out.

“The problem we’re facing for these new technologies is the lack of evidence on how best to use them – we still don’t know the full benefits they can offer,” Harrington explains. “And without this evidence, we simply don’t know which patients should be treated by them.”

Their plan is also to develop guidelines on the best way to test the new techniques – such as the best dose and number of treatments – that can be used across the UK. Having these guidelines will help researchers compare results from clinical trials from different centres.

“We’d like to see radiotherapy becoming more targeted so we can give bigger doses in fewer treatments,” says Harrington. “Not only is this quicker and easier for patients, but it’s more effective at destroying cancer and saves the NHS money too.”

Another reason this research is vital is that many of the NHS’ standard radiotherapy machines are getting old and need replacing.

The question Harrington is pondering is whether these machines should be replaced ‘like for like’, or is there something better?

“That’s what our research is setting out to determine,” he explains. “It’s vital we make the right choice for patients.”

Understanding brain tumours

Survival for many types of cancer has improved dramatically over the last 40 years, but this hasn’t been the case for brain tumours. Progress has lagged behind, and it’s clear we need to do more.

And the final award will be going to Edinburgh to focus on gliomas – the most common type of brain tumour. Dr Steven Pollard, who’s leading the project, sees it as an amazing opportunity to set up a crucial resource that is desperately needed for scientists to study the disease.

We have the opportunity to get an unprecedented level of genetic and molecular detail, enabling us to create a complete catalogue of the different types of brain tumours

– Dr Steven Pollard

“It’s not always been easy getting funding to study brain tumours, or enough young scientists wanting to work in this area,” he explains.

“The situation is happily improving, and this award will really help us with the fundamental work we need to carry out – getting high quality samples to study.”

They will be using their expertise to create a large collection of different types of brain tumour cells donated by patients during surgery.

They will then be able to grow and study these cells in the lab, which has two big advantages, as Pollard explains: “First, classic ‘cell lines’ that are often used in lab experiments have changed at the genetic level over time, so they no longer accurately represent human disease.

“And second, we have the opportunity to get an unprecedented level of genetic and molecular detail, enabling us to create a complete catalogue of the different types of brain tumours. This detailed information will be available to other researchers, and will be really useful to help drive new drug discovery studies.”.

The project needs a lot of technical support – research nurses and lab technicians to collect and grow the samples, as well as skilled lab and computational biologists to identify and analyse the molecular and genetic faults at play.  They will be working closely with teams at University College London, and Pollard believes this systematic and joined-up approach will be crucial in understanding the biology of the disease, and coming up with new ways to treat it.

“In five years’ time, we want to have all the tools needed to drive forward scientific research into gliomas around the world,” he says.

“Studying these tumour cells will kick start new projects and collaborations, bringing together scientists and industry. This is a vital step towards developing better treatments for patients.”

The four awards will build up the resources, skills and infrastructure that are needed to maximise the potential of immunotherapy and radiotherapy, grow understanding of the biology underpinning brain tumours, and gather more complete information on how cancer changes up to and at the point of death.

Giving researchers the tools and samples they need to make progress against cancer is vital.

The research that could follows from these Awards could have a big impact on treatment for cancer patients, particularly for types of cancer where survival is still poor.

Emma