Stem cells could hold the key to beating bowel cancer

By Henry Scowcroft  

Why do some cancers come back, even after surgery and intensive chemotherapy? 

It’s a fundamental question. And at the UCL Cancer Institute in London, Cancer Research UK’s Professor Christopher Tape is closing in on answers. Tape’s lab at UCL studies how cancer cells interact with their surroundings – collectively referred to as a tumour’s microenvironment. 

“Normal cells are essentially controlled by two things: their genes and signals from their environment”, says Tape. “In cancer, a growing tumour is a unique mixture of cancer cells – which have damaged genes – and healthy cells, and my lab is interested in understanding how all these cells communicate to drive bowel cancer.” 

One way cells communicate is by releasing chemical signals which are absorbed by their neighbours, which then, in turn, triggers a cascade of internal molecular changes causing them to change behaviour. But studying these signalling networks can be fiendishly tricky. 

“Until a few years ago, to do this we used to grow cancer cells in a Petri dish, grind them all up and try measure what’s going on inside all of them at once,” says Tape. “This simplistic approach worked to some extent, but it missed a lot of important details. It was a bit like trying to figure out exactly what was in a fruit bowl by analysing a smoothie. 

“To properly understand what makes a tumour tick, we needed two things: a way to grow patients’ cancer cells in a 3D, tumour-like environment; and a way to measure these cells individually.” 

Bowels in a dish 

The solution to the first problem arrived in the early 2010s, when researchers in the Netherlands developed a completely new way to study living systems: organoids. 

“Organoids are microscopic, three-dimensional models for studying how cells self-organise into tissues,” says Tape. They’re created from specialised cells called stem cells. When these cells divide, one of the resulting ‘daughter’ cells remains a stem cell, but the other can change into different kinds of cells in the body. In doing so, stem cells help the body grow, and repair damaged tissues. And research has shown that rogue stem cells are particularly important in cancer, fuelling a tumour’s growth by endlessly churning out new cancer cells. 

The Netherlands researchers had isolated stem cells from gut tissue and found a way to encourage them to form microscopic gut-like structures, made of just a few thousand cells, that recreated many of the cellular structures found in a healthy bowel. Crucially, they also showed how stem cells from patients’ bowel tumours could be grown into miniature bowel cancers. 

When he first heard about organoids, Tape was intrigued by their potential for studying cell communication in cancer. “Organoids are much cheaper and easier to work with than animal models like mice. Working out how to study them at scale would be a powerful way to run thousands of experiments on cells from dozens of patient’s tumours,” he says.  

At around the same time, tragically, Tape’s mentor – world-renowned cancer researcher Professor Chris Marshall – developed incurable bowel cancer himself. “My grandmother died of bowel cancer when I was a teenager, so seeing a scientific legend like Chris experience a similar fate really brought bowel cancer to the forefront for me” says Tape. “At the time no one really understood the tumour microenvironment in bowel cancer, but it was clear that it was very important, and I couldn’t stop thinking about it.” 

Alongside organoids, another technological revolution was emerging, allowing scientists to study individual cancer cells one at a time. “It’s been an absolute game-changer for cancer research,” says Tape. “Tumours are ecosystems of millions of interacting cells and now we have the technologies to see what every cell is doing.” 

Central to Chris’s work is a powerful machine known as a CyTOF, which allows organoids to be broken down and analysed one cell at a time. This means researchers can grow multiple different samples of identical organoids under different conditions, then use the CyTOF to measure how each condition changes how organoids behave, including changes in multiple different signalling molecules inside their cells. Crucially, it allows them to do this at a scale and speed that would be impossible using animal models. 

This scale becomes even more powerful when applied to organoids grown from different patients’ tumours. And because no two patients have identical tumours, this has allowed Chris’s team to start to decipher the underlying rules that govern how bowel cancers respond to treatment. 

A stem cell revival 

Through crunching data from millions of cells from thousands of experiments on different patient organoids, Tape’s team have started to reveal why some cancers are able to return after treatments like chemotherapy and radiotherapy. And key to this has been the breakthrough discovery of an entirely new type of stem cell inside bowel tumours 

“Normally, bowel cancer stem cells are so-called ‘proliferative’ stem cells. These are similar to healthy gut stem cells, but ‘turned up to 11’ by the DNA mutations they carry,” Tape says. “They’re what you classically think of as cancer cells. 

“But we’ve discovered that bowel cancer cells aren’t always like this. In fact, they can change very quickly into so-called ‘revival’ stem cells – normally, this is a survival state that the bowel enters following damage or infection. It seems that bowel cancer cells can ‘remember’ how to access this state and use it to their advantage.” 

Crucially, these revival cells are stubbornly resistant to chemotherapy or radiotherapy. “It’s relatively easy to kill fast-growing cancer cells – it’s how chemo and radiotherapy work” says Tape. “But revival stem cells slow down their growth, so treatments don’t work on them.” 

Tape’s team have shown that different patients’ stem cells seem to differ in how easily they flip into a revival state – providing an explanation for why some patients’ cancers come back after treatment. Crucially, they’ve also discovered that signals from other cells in the tumour microenvironment, called fibroblasts, are responsible for flipping fast-growing cancer cells into the revival state. Ultimately, Tape thinks finding a way to specifically target revival stem cells could revolutionise how bowel cancer is treated, preventing the disease from returning after therapy and, potentially, curing it. 

“My lab is basically at war with these cells now,” he says, and they’re now working on strategies to block, target, and kill them. 

TAILORing treatment to beat cancer 

Since these discoveries, we’ve awarded Tape £1.5m funding to find out more about the communication networks that trigger the revival stem cell state, through a programme called TAILOR. 

“We want to uncover the fundamental rules behind why different patients respond differently – and that means analysing organoids from lots of patients,” Tape explains.  

As part of this project, his colleague Petra Vlckova from Cancer Research UK City of London Centre’s Organoid Platform will collect samples from 50 people who’ve had surgery for bowel cancer at UCL Hospital (UCLH). This includes taking samples of their stem cells, to create cancer organoids, but also neighbouring fibroblasts to help decipher the cellular cross-talk, and healthy tissue and blood to build a complete picture of each patient’s disease. “The Organoid Platform acts as a bridge to connect patients in the NHS with cutting edge laboratory science” says Vlckova. “Programmes like TAILOR will fundamentally change our understanding of bowel cancer.” 

One of the people whose samples are powering TAILOR is Sharon, who recently had a bowel tumour removed by the surgeons at UCLH. It was her second operation – she’d initially been diagnosed in 2023, and had surgery and chemo at the time. But in January 2025, a second small tumour was spotted at a follow-up appointment. 

“When Petra approached me to take part, it was a no-brainer,” Sharon says. “I said, ‘whatever you want, you can have it. I don’t need it anymore!’ The idea that my cancer cells are growing in a lab somewhere, helping researchers… it’s just incredible.” 

And Sharon’s clear about the power of research to improve treatment. 12 years ago, her sister was treated for cancer, and her brother – who has now accompanied both his sisters for their treatment – remarked to her how things had changed over that time. “The change in just 12 years has been incredible,” she says. 

Chris sees even more changes ahead. “Five years ago we didn’t even know revival stem cells existed. Now it looks like they’re behind everything bad about bowel cancer – drug resistance, spread, and relapse. But to learn their tricks, we need to see them in action – that’s why patients like Sharon are so fundamentally important. Their cancers will teach us how to beat future cancers. 

“I think in 10 years’ time bowel cancer treatment will be very different. It’s going to take time for the trials to be done and the progress to be made, but we’re going to find a way to kill these cells,” he says. “We won’t stop until we do.”