Credit: Imperial science imagery
This entry is part 17 of 25 in the series Cancer Grand Challenges
Today, we’re announcing 3 new teams who are tackling some of the toughest questions in cancer research.
They’ve been brought together by our most ambitious research award, Grand Challenge. It was set up back in 2014 to revolutionise our understanding of cancer and make big strides towards better treatments and new ways to prevent and diagnose the disease.
And Margaret Grayson, who is part of the patient panel that evaluates applications, has been there from the start.
“I remember being in Edinburgh for the very first meeting. I was sitting around a table with oncologists, basic scientists, engineers and mathematicians – all experts in their field. And it dawned on me that this is what a Grand Challenge is, bringing people from around the world and from different disciplines together, some of whom might never have met if it weren’t for this award, to tackle some of the biggest questions in cancer research.”
Two years ago, we challenged 4 international teams to uncover previously unknown causes of cancer, develop new ways to map cancers and find ways to spare women unnecessary treatment for breast cancer.
But we haven’t stopped there. Last year we launched the second round of Grand Challenge, with 8 new problems for scientists to tackle.
“The strength of the applications this time round was quite overwhelming. It’s phenomenal to see that amount of thinking and work that goes into them,” says Grayson.
And we now have 3 new international teams who are stepping up to the challenge. Together, they’ll receive up to £60 million over the next 5 years.
“All three projects are amazing, there’s something in each of them that drew the panel to them. And they’re all such incredible teams,” says Grayson.
We’ll be taking a closer look at all 3 teams in the next few months. But for now, meet the newest Grand Challenge scientists.
Professor Matthew Meyerson and Professor Wendy Garrett – Can we use gut microbes to improve cancer treatment?
Our bodies are home to trillions of different microorganisms, which together form communities called the microbiome, or microbiota. And the largest of these communities, formed mostly of bacteria, is found in the gut.
While these microbes play important roles in keeping our bodies healthy, scientists have also found that gut bacteria appear to play a role in how some cancers develop. And potentially how some patients’ cancers respond to certain treatments. But it’s not entirely clear how. And that’s what this ambitious Grand Challenge project is aiming to change, focusing initially on bowel cancer.
Professor Matthew Meyerson, from the Dana-Farber Cancer Institute and Harvard Medical School, and Professor Wendy Garrett, from the Harvard T.H. Chan School of Public Health, are heading up a team of experts based in the US, UK, Canada, the Netherlands and Spain.
“We’re starting with the question of bowel cancer risk,” says Meyerson. “Do some bacteria found in the gut actually affect the risk of getting cancer? And if the answer is yes, then how?”
To do this, the team will analyse microbiome samples from over 17,500 patients, studying how particular species of bacteria might affect how tumours develop and grow. And they’ll look at how risk factors for cancer, like diet, smoking and environmental exposures, affect the gut microbiome and how that could affect someone’s bowel cancer risk.
The team is also hoping to unpick how the gut microbiome might change how cancers respond to treatments like immunotherapy and chemotherapy. To do this, they’ll be taking samples of healthy bowel tissue and bowel cancer and growing them in a dish to form mini bowels, called organoids.
“We’re lucky to have Hans Clevers on our team, who pioneered the technique of making organoids,” says Garrett. “These models allow us to study how the cells behave in great detail in the lab.”
Last, but by no means least, the team will test if changing the gut microbiome can help to treat bowel cancer. Depending on how their initial studies go, the team hopes to launch one or more clinical trials testing potential new treatments, which could include an antibiotic therapy, a vaccine and/or the introduction of beneficial microbes.
“Our long-term hope would be to see microbiome targeted therapies that could benefit patients with bowel cancer,” says Meyerson. “We’re not going to be able to achieve that in 5 years, but we’re aiming to make progress in that direction.”
Professor Stephen Elledge – Why do some faulty genes only cause cancer in certain parts of the body?
Different mistakes in DNA can cause different types of cancer. Faults in a gene called APC can cause bowel cancer, for example. And another gene called BRAF goes wrong in around half of melanomas.
But what scientists don’t know is why some errors cause cancer in specific organs and not others. And that’s what Professor Stephen Elledge, from the Brigham and Women’s Hospital at Harvard Medical School, and his team of scientists based in the US, UK and the Netherlands, aim to find out.
“It’s always been a big puzzle in the scientific community as to why different cancers are using different genes,” says Elledge.
Elledge has been interested in this genetic conundrum for a long time. And thanks to Grand Challenge, he has been able to assemble the team, part-funded by New York-based philanthropic organisation The Mark Foundation for Cancer Research, to help him solve it.
“Most people have tried to answer this question by looking at cancer cells,” says Elledge. “But they’ve got so many different changes to their DNA, it’s hard to figure out what’s doing what. If we take a normal cell with a pristine genome and turn a particular gene on or off and look what it does, we can start to see differences in how cells from different parts of the body behave.”
Elledge and his team will take healthy cells from 8 different tissues, including the bowel, lung, kidney and skin, and introduce faults found in cancer cells. They’ll then study how the different cells behave, looking at changes in how the cell’s DNA is read and what proteins are produced.
They’ll also work with organoids and mouse models to study certain DNA changes in unprecedented detail.
Together, these experiments will help to map out where in the body certain faults help cancers grow and where they don’t. And it’s this combined approach that sets the project apart.
“If you’re not looking at everything together side by side, you can’t see the full picture,” says Elledge. “Once we have that it could open up new treatment avenues, by telling us which faults we might want to target and how.”
“We could never get this many people together to work on something like this if it weren’t for Grand Challenge.”
Professor Thea Tlsty – How does chronic inflammation cause cancer?
The link between inflammation and cancer was made back in 1863, when a German pathologist observed immune cells within tumour samples. But over 150 years later, we still don’t fully understand how inflammation can help cancer to develop and grow.
“Around 1 in 4 cancers start with chronic inflammation. These cancers tend to be the most aggressive – the ones that are most likely to spread and that don’t have effective therapies to treat them,” says Professor Thea Tlsty, a pathology expert from the University of California in the US.
Tlsty and her team of Grand Challenge scientists, based in the US, UK, Canada and Israel, believe that a shared mechanism might be behind these cancers, and by understanding how they develop, they can open up new avenues to help prevent and treat these diseases.
“We’ve got some early data that suggests it’s the interaction between cells within a tissue that makes the difference,” says Tlsty.
So far, they’ve found a role for a group of cells called stromal cells, which support and organise tissues within the body. And Tlsty believes that changes in these cells encourage inflammation and might cause tumours to grow.
“We have data indicating that if you put the stroma in a certain state, it can actually stop cancer from growing,” says Tlsty. “We want to find out how to get the stroma into this state and keep it there.”
The team will use sophisticated imaging techniques to see how stromal cells change in the oesophagus, colon, stomach and lung and listen in on the molecular chatter between different cell types. By understanding the link between inflammation and cancer, they want to find ways to block or reverse the process.
“We’re hoping to have an impact from the beginning of the disease – looking at prevention and early detection – to the very end in the form of new treatments,” says Tlsty.
Changing the outlook for people with cancer
Together, these 3 teams want to revolutionise the way we look at and treat cancer.
“What’s special about Grand Challenge is not just the amount of money, but the type of research that’s being funded. It supports areas of research that ask the big questions about cancer,” says Grayson.
“To even be a small part of something as big and ambitious as this is quite an amazing feeling. It’s been a real privilege.”