The first episode of the series follows Sarah, Professor of Experimental Oncology in the Department of Oncology, who is leading novel precision prevention cancer research at the University of Oxford. This approach uses genetic and biological information to understand the earliest changes that cells go through on their journey towards becoming cancerous.
Precision prevention trials test treatments that target these changes to stop cancer before it becomes established. Unlike traditional prevention studies, which take years to yield results in unselected populations, precision-prevention studies are focused on high-risk groups, for example, people with rare genetic cancer predispositions. Samples are collected to give a deeper understanding of how cancers develop, and insights from precision prevention studies can also be applied to cancers in the general population.
Metformin in Li Fraumeni Syndrome
Sarah’s episode introduces us to 26-year-old Ella, who is living with Li Fraumeni Syndrome (LFS), a rare genetic condition that gives her a >90% lifetime risk of developing multiple cancers, particularly those of the brain, breast, blood and soft tissue. Ella has already experienced two cancers in her lifetime.
Currently, the only option for people with LFS is to undergo intensive regular screening in the hope of catching and treating emerging cancers as early as possible. However, this “watch and wait” strategy can create a high level of anxiety among patients with LFS and their families.
Ella hopes to join Sarah’s Metformin in Li Fraumeni Syndrome (MILI) trial, which launched in early 2024 and was the first precision prevention trial led by the Oxford CRUK CTU. MILI aims to recruit 200 participants to investigate whether the commonly used type 2 diabetes drug metformin can prevent or delay cancer in people with LFS.
If successful, metformin could be the first cancer intervention available for those with LFS as, until now, no preventive drugs have ever been tested in this condition. The research will also help the team to understand more about how cancer may be prevented in the general population.
Speaking about the trial in a recent interview with Cancer Research UK, Ella said:
“Meeting Professor Blagden while filming this documentary and seeing the research that’s going into my condition is very reassuring. It’s not just helping people like me, it’s helping future generations.
“It's been a really positive experience being part of the programme and I hope as many people as possible will watch it. I love medical documentaries anyway but to feature in something so important and inspiring, to shine a light on Li Fraumeni syndrome and meet the team trying to help manage it, has been a real privilege. They're helping to create a world where cancer doesn’t win.”
LungVax
The episode also follows Sarah’s efforts to secure funding for a clinical trial of LungVax, a pioneering vaccine designed to prevent lung cancer in people at high risk of the disease.
Each year, around 48,500 people are diagnosed with lung cancer in the UK. Around 72% of cases are caused by smoking, the leading preventable cause of cancer worldwide.
The LungVax vaccine carries a series of genetic instructions which train the immune system to recognise tumour antigens on the surface of abnormal lung cells. In trialling the vaccine, the aim is to get the immune system to recognise these early abnormal antigens, and kill the cells before they start to become cancer. The vaccine uses the ChAdOx vaccine vector, developed by the University of Oxford and originally used for the Oxford/AstraZeneca COVID-19 vaccine, to deliver these instructions to the immune system.
It was announced last week that Sarah and her team, including coinvestigators from the TRACERx team at University College London’s Crick Institute, have been awarded £2.06 million from Cancer Research UK, supported by the CRIS Cancer Foundation, to run a precision prevention trial of LungVax over the next four years. If the trial delivers promising results, the vaccine could then be scaled up to larger trials for people at risk of lung cancer.
Commenting on the news, Sarah said:
‘Lung cancer is lethal and blights far too many lives. Survival has been stubbornly poor for decades. LungVax is our chance to do something to actively prevent this disease. Years of research into the biology of cancer, understanding the fundamental changes which occur in the very earliest stages of the disease, will now be put to the test. This funding means that, for the first time, we hope that people will be able to receive LungVax in a clinical trial from next year.’
NuTide 701
Beyond prevention, Sarah’s work also investigates new treatments for patients with existing, advanced cancers.
In the episode we meet Trevor, a retired Navy veteran whose skin cancer has spread to his liver and who is receiving experimental treatment at Oxford University Hospitals Early Phase Trials Unit as part of the NuTide 701 trial.
NuTide 701 is a trial designed to establish the efficacy of a potential new cancer drug called NUC-7738 given with immunotherapy for people with advanced cancers. Results in people with melanoma have been promising, demonstrating that the drug can boost the response to immunotherapy, even in patients who have failed to respond it in the past.
You can follow Trevor and Ella's stories in Sarah’s episode of Cancer Detectives: Finding the Cures, now streaming on Channel 4.
You can also read the Guardian's four star review of the documentary in The Guardian Online.
Find out more about the University’s precision prevention work on the OxCODE website.
Photo Credit: Professor of Experimental Oncology at the University of Oxford, Sarah Blagden, features in new Channel 4 documentary series Cancer Detectives: Finding the Cures, is available to stream or watch on Channel 4, in partnership with Cancer Research UK.