Press Pack Interview with Professor Caroline Dive for Episode 3

In the show, you describe yourself as “a detective in the cancer world trying to outfox cancer.” What first inspired you to take on that challenge?

I enjoyed science at school, especially biology. I did a Pharmacy degree partly because I was interested in science, but also because my dad grew up poor and wanted me to be able to enter a well-paid profession! After my pharmacy training, I began to think seriously about what I wanted to do as a long-term career. The death of my maternal grandfather, whom I never met, from brain cancer and the devastating impact it had on my mum was a strong motivator to pursue cancer research. That led me to seek PhD positions, and I was lucky enough to secure a studentship with Professor Paul Workman in Cambridge to study how drugs are used to treat cancer. That got me hooked! For more than a decade, I studied how cancers resist drug treatment. In 2004, I moved to the Cancer Research UK Manchester Institute to set up a new biomarker centre, focused on finding new ways to measure what’s going wrong in cancer, to develop tests to optimise patients’ treatment and to detect the cancers earlier. The rest is history.

You mention that you’d been thinking about how to fight cancer since you were 25. What was the moment that set you on this particular path of research?

There have been several ‘moments.’ The first was back in the 1980s during my PhD, when I was studying how diverse cancer cells inside one tumour can be, and I began to grasp the complexity of the disease. The second came in Birmingham, when we realised cancer cells could avoid being destroyed by our body’s natural cell-death programme, which is key to how they resist treatment. The third came more than 20 years ago, when personalised cancer medicines were in their infancy, and Professor Nic Jones suggested I come to the Cancer Research UK Manchester Institute to set up a Cancer Biomarker Centre. That was visionary, exciting and daunting!

For those unfamiliar with your work, how can a blood test reveal the presence of cancer, sometimes even before a scan can? What is the test picking up?

Detecting cancers early through a blood test, before they’d appear on a scan, is a huge global ambition. While progress is being made, it remains a considerable challenge, with some cancer types proving much harder to detect than others. We look for many different types of molecules in the blood but we typically study fragments of DNA shed by dying cancer cells, called circulating tumour DNA. These DNA fragments can be analysed using different scientific techniques to spot signs of cancer, such as sequencing for cancer-associated mutations or assessing DNA fragment lengths that distinguish cancer cells from normal ones. Some new technologies are sensitive enough to detect signs of cancer that are present in really low amounts in the blood. But creating a test that is sensitive and specific enough to reliably detect all early cancers is a huge challenge and should not be underestimated.

You speak about the challenge of detecting cancer at its earliest possible stage. What signs of “pre-cancer” are you looking for, and how close are we to detecting them?

A pre-cancer is a group of abnormal cells that have the potential to turn into cancer but aren’t cancer cells yet. Most scientist I think  that  changes in the immune system are likely to be  early signs of a pre-cancer developing into cancer. The challenge is distinguishing which immune changes are linked to cancer and which could be caused by something else, such as a common cold. So, I think we’re still some way off having a blood test for this. But, we’re working on blood tests to detect DNA from cancer cells and immune cells that could tell us more about if cancers developing. We’ll see how that progresses.

You’ve described detecting cancer DNA in the blood as “finding a single grain of sand among millions.” What breakthroughs in technology now makes that possible?

Recent breakthroughs in circulating tumour DNA detection have come from new technologies, including DNA sequencing technologies that let us ‘read’ our genetic code, comprehensive map-like databases of all the different types of cells in our bodies, and libraries of information about our genomes – our full DNA sequence - built over the past decade, plus the rise of advanced computing tools and AI capabilities. 

You mention clues in the blood that tell you how a cancer cell is behaving and what its next move is. What exactly are these clues, and how do they tell you that?

One hallmark of cancer is its ability to change and gain new abilities like spreading through the body, taking root in unfamiliar tissues, and colonising them. We call this cancer plasticity. By studying circulating tumour DNA and specific chemical modifications to it, we can chart these changes that are like “shape-shifting”. We might even in the future be able to predict how cancer cells will behave. These are some of the methods we’re developing at the Cancer Research UK National Biomarker Centre. 

The idea of a “liquid biopsy” is transformative. How does this approach differ from a traditional tumour biopsy, and why is it less invasive for patients?

A liquid biopsy involves taking a sample of a bodily fluid in a minimally invasive way. For example, a simple blood draw from the arm or a sample of urine or spit, rather than a surgical procedure to remove tumour tissue, which can be risky and depends on tumour location (skin versus lung versus liver, for example).

These biological fluids are then analysed for cancer-related molecules that could serve as biomarkers – early warning signs of cancer and clues to cancer’s behaviour – to detect the disease early and to guide patient treatment. 

Your research suggests that spotting signs of cancer in the bloodstream could extend – or even save – lives. How close are we to seeing this test in everyday clinical use?

There’s no one-size-fits-all answer to that. Some liquid biopsies are already in routine use in the NHS. For example, a test that involves analysing circulating tumour DNA is currently helping doctors select the best treatments for people with lung cancer orbreast cancer. Other liquid biopsies are in various stages of development, and we must test them rigorously, in large enough clinical trials, to ensure they truly work before they’re deployed routinely. We also need to avoid overpromising or using them in ways that might lead to overtreatment.

You’ve said, “You have to know your enemy to have a good fight.” What are the most important things to know about cancer, and what are you learning about how cancers behave and spread that could change how we treat them?

By “knowing your enemy,” I mean that having an in-depth biological understanding of cancer is essential if we want to make meaningful progress that improves survival of patients. Cancer Research UK-funded studies such as TRACERx have shown that lung cancers evolve over time, that treatment can shape this evolution, and this can result in treatments not working. But by studying these changes in detail, we can begin to identify patterns (AI will play a key role here) and predict how a tumour, and even its surrounding tissue, might change as it becomes more complex and therapy-resistant.

That’s also why detecting and treating cancers earlier, before such evolution occurs, is so important.

One of your projects is CUPiD (Cancer of Unknown Primary Identifier), designed to identify where a cancer began. How could this improve outcomes for people with cancers of unknown primary?

As the name suggests, cancers of unknown primary (CUP) are true mysteries where patients have metastatic tumours (cancers that have spread from one part of the body to another), but no one knows where the first tumour developed. We’re acting as cancer detectives, aiming to rapidly diagnose where a cancer started so that, combined with other molecular and clinical data, the patient can receive the right treatment for their disease. Currently, diagnosis can take many months, leaving patients aware they have advanced cancer but not what kind. This means a “one-size-fits-all” treatment approach is used and people often won’t have much time after their diagnosis. We want to develop and validate the CUPiD test as quickly as possible to give patients an accurate diagnosis earlier so they can begin personalised treatment as soon as possible that has a better chance of controlling their disease.

You talk about tumour cells having a “postcode,” which allows you to determine where they came from. What exactly is this postcode, and how do you detect it?

Every normal tissue cell has a DNA identity, a chemical ‘annotation’ profile, that tells us what type of cell it is. Genes required for a tissue’s specific functions are switched on or off via a process called DNA methylation, which adds chemicals called methyl groups to DNA. These methylation patterns differ by tissue type, for example, liver cells versus brain, gut, or lung cells. We can measure these patterns on DNA fragments shed from tumours in blood samples from CUP patients. This gives us a molecular “postcode” indicating the tissue where the cancer started before it spread elsewhere.

What stage is the CUPiD test at now? How far off are we from seeing it in the clinic?

Getting CUPiD into clinics takes a lot of hard work. We first train the test using cancers with known origins to create a “postcode” for each tumour type. We’ve done this for several cancers already, but we need to repeat these experiments many times to make sure it’s robust. Every step of the lab process and every “postcode” must be rigorously validated. Then we’ll test CUPiD in large clinical trials to confirm that it speeds up diagnosis and helps patients. This process takes longer when the original cancer is a rare type. Finally, we’ll likely partner with a biotech company to scale up the test for routine use. It will take several more years, but I’m confident CUPiD will make a real difference for CUP patients in the mid-term future.

How has working alongside clinicians at The Christie Hospital in Manchester helped accelerate discoveries at the Cancer Research UK National Biomarker Centre?

The location of the Cancer Research UK National Biomarker Centre at The Christie Hospital is absolutely pivotal to our success. Over the past 20 years, I’ve built strong collaborations with many brilliant oncologists there. This collaboration is crucial at every level, from identifying key clinical questions and accessing patient samples to designing innovative trials that test biomarker performance. Cooperation and mutual respect between scientists and clinicians, combining expertise, networks, and ideas, are essential for progress. Equally important are our interactions with patients and their families. Their voices and lived experiences are invaluable in shaping how we conduct our research.

How crucial has support from Cancer Research UK been in enabling you and your colleagues to push the boundaries of what’s possible in early cancer detection?

All our early detection research in lung cancer has been supported by Cancer Research UK. We’ve worked alongside colleagues in Manchester developing community-based screening with “scans in vans” in supermarket car parks. Even when our lab was destroyed by fire, Cancer Research UK’s support allowed us to continue collecting and storing blood samples. We’re now working with colleagues in the US, using these samples to develop a blood test that could enhance lung cancer screening. It’s ambitious, but we’re making progress.

Your work depends on patients like Lee and Damian, who are both featured in the Channel 4 documentary, donating their blood samples. What does their participation, and that of others, mean to you and your team personally?

I cannot praise or thank patients like Lee and Damian enough. Even while facing their own cancer journeys, they volunteer to help us advance biomarker research, and they do so with incredible enthusiasm. It’s truly humbling and makes us want to work even harder and faster to make an impact.

You’ve talked about growing up in Sussex and how your father instilled a love of learning. How has that early influence shaped your drive and determination today?

My dad grew up poor. His mother died young, his father disappeared, and he and his two younger brothers were raised by their strict grandmother. Despite lacking a formal education himself, he valued learning deeply and made it a priority for his children. He devoted all his spare time to teaching us the joy of learning, especially history, his favourite subject. From him I learned self-discipline, organisation, competitiveness, and determination. Every night he’d ask, “Caroline, what did you learn today?” I still ask myself that question before I fall asleep. My proudest day, receiving my CBE when Dad was still alive, was in recognition of all his care and encouragement.

You mention that your father died from a cancer of unknown primary. How did this experience shape your research journey?

My dad lived a long life; he was 95 when he passed away, but CUP was listed on his death certificate, with tumours filling his liver. We were already working on CUP by that point, but witnessing his truly final months first-hand gave me even more determination to make a difference for future patients.

You’ve called this “the golden age of cancer research.” What gives you the greatest sense of optimism about the years ahead?

Looking back over 25 years in cancer research, I’m struck by how much progress has been made, from understanding cancer biology to developing targeted therapies. The pace of discovery is accelerating, and that gives me great optimism. With technological advances and the careful application of AI, I believe we can achieve even more, though we must not underestimate the challenges. Early detection and treatment remain key. To continue making real progress, we need greater investment, more training opportunities for young scientists and clinicians, and closer collaboration with the pharmaceutical and biotech sectors.

Finally, what would you like people to take away from watching the Channel 4 series, and if they feel inspired, how can they play a part in supporting this kind of research?

I hope viewers gain meaningful insight into the lives and work of cancer researchers and feel excited about what we do and why it matters. When members of the public visit my centre, it’s a joy to see their fascination with our work. I hope the series will amplify understanding of both the challenges and the thrill of discovery, and how research translates into better patient outcomes. Cancer affects us all, directly or indirectly, and that impact will only increase as populations age. I hope the series helps families better understand cancer care and treatment, and that the stories inspire people to get involved in research or fundraising. I also hope it inspires young people to consider careers in cancer research. I feel privileged to have been supported by Cancer Research UK throughout almost my entire career.

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