Image credit: Jeroen Claus / Phospho Biomedical Animation
Joanna Lewin delves into the fascinating world of TRACERx – the first longitudinal, large-scale study of lung cancer evolution – and explores how long-term philanthropic support has led to explosive new discoveries.
Half a decade ago, a new cancer research project emerged that would help propel our understanding of cancer evolution in ways never imagined before. The nine-year, £12.5m study, named TRACERx (Tracking Cancer Evolution through therapy [Rx]) and funded by Cancer Research UK, allows researchers to break free from the confines of studying a snapshot of cancer on a microscope slide and instead examine the complex process of cancer evolution as it occurs inside the body over time. As this unique project caught the attention of enthusiastic scientists up and down the country – it employs 225 researchers – so too did it capture the imagination of a group of visionary philanthropists who saw its abundant potential. Many of them still regularly donate to the project, with newer supporters joining along the way.
As TRACERx celebrates its fifth birthday with two brand new research papers, and science journal Nature cements the project’s world-leading status by featuring all eight of its published papers in a special edition, we take a look at how the project has flourished thanks to sustained philanthropic support – and how COVID-19 poses a threat to its continued success.
What exactly is TRACERx and why does it matter to cancer patients globally?
At the project’s core sits a basic premise: not all cancer cells within a tumour are the same, which means that single biopsies used for diagnosis might not show all the defects present in the tumour cells. What’s more, tumours often evolve over time, which ultimately leads to drug resistance and treatment failure. This is possibly the single-biggest clinical challenge in cancer research.
In the face of this challenge, Cancer Research UK’s Chief Clinician, Professor Charles Swanton, secured our largest ever single investment in lung cancer research in 2014 to establish a new project to study the evolution of the disease in unprecedented detail. The aim is to understand more about how tumour cells differ from one another and how they change incrementally. Before the coronavirus pandemic, the project had enrolled 760 people with early-stage non-small cell lung cancer, each of whom has been monitored for genetic changes to their tumour over time.
Already, exciting results are emerging. Thanks to TRACERx, researchers can now predict whose lung cancer will return after surgery by detecting tumour DNA in their blood and who may need additional therapy after surgery to help prevent the disease returning. They can also develop tests that use machine learning to predict clinical outcomes at the point of diagnosis. And, like town planners mapping out high- and low-density population urban areas, scientists can now use AI to chart regions in a tumour where immune cells are highly concentrated – vital knowledge, as it turns out, for predicting the outcome of a patient with lung cancer.
This is not an exhaustive list of findings. Eight seminal papers have been published by TRACERx researchers in just five years – each one shining light on previously opaque areas of understanding. Due to sustained and strategic funding provided by philanthropic supporters, researchers are able to venture down multiple important avenues of research, which are integrated with others and considered holistically, rather than separately. Some of these supporters are members of our giving circle, the Catalyst Club, which connects philanthropic investors with pioneering scientists to help us respond to areas of urgent scientific need and drive progress at speed and scale.
The importance of innovation
Vanessa Marsland is a partner at international law firm Clifford Chance and a Catalyst Club member. She learnt about TRACERx at an event held at her London office. “I work in intellectual property, so I know the importance of innovation,” she says. “Hearing Charlie [Swanton] speak at the event was very inspirational and I wanted to help.”
But it wasn’t just the ingenuity and innovation on display that compelled her to get involved. Vanessa lost her father to prostate cancer, which was diagnosed at a very late stage. Her father-in-law lost his first wife to breast cancer and his second wife to oesophageal cancer. And one of her children is a leukaemia survivor. This onslaught of the disease against her family has driven Vanessa’s motivation to support the early detection of cancer – specifically hard-to-treat cancers, such as lung cancer. “The early detection element was particularly interesting to me,” she says. “I was also impressed by the project’s scale. I’m not sure other charities or organisations could support such a large initiative over time, so it’s marvellous that Cancer Research UK has brought it so far.”
With a library of key findings to the project’s name already, we can only imagine what new discoveries will be made in the next four years. But the reality is, with Cancer Research UK’s income projected to fall by 20-25% this year and cuts to funding totalling £44m so far, projects such as TRACERx are at risk. COVID-19 will take a serious toll.
Ensuring progress can continue
For Vanessa, it’s vital that projects offering the world such important insight continue. “I’ve come to see over the years that it’s the long-term studies that will help more people survive cancer,” she says. “The need to invest in research hasn’t gone away, but givers have been temporarily distracted. We need to be thinking about the people who have had their treatments stopped or whose diagnoses have been delayed during this pandemic. But we also need to look to the future and make sure progress can continue.”
Professor Swanton agrees. “Through TRACERx, not only have we found new ways to predict clinical outcomes, but we can now detect when lung cancer has returned before it’s seen on a scan and how the tumour evades the immune system,” he beams. “New cutting-edge treatments that use a patient’s own immune cells that have been reprogrammed to target lung cancer cells could become a reality.
“However, COVID-19 has dealt a severe blow. Clinical trials have stopped across the country and patients are quite rightly being discouraged from coming to hospital if possible. We have more than 300 patients on the study at the moment, none of whom can be followed up with the necessary clinic visits, blood tests or biopsies. In all likelihood, we will have to recruit several hundred additional patients to compensate for the loss of follow-up data.”
“Ultimately,” says Vanessa, “more people will suffer due to research having been delayed. The sooner Cancer Research UK can scale up again, the better for us all.”
TRACERx and its discoveries demonstrate the power of philanthropy.
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– by Joanna Lewin, Philanthropy Editor