“A clinical trial gives hope,” says Steph. “It brings this overwhelming sense that people care, that they’re saying, ‘This isn’t acceptable’, and that they want to do something about it. Scans are really important, but getting ahead of cancer and asking how we can prevent it is literally lifechanging.”
What’s metformin? How could it help?
Animal research has shown that metformin, the drug being tested in the MILI trial, can keep mice with TP53 mutations cancer-free for longer. We know it’s safe to use because it’s one of the most common treatments for type 2 diabetes. Smaller, short-term studies have shown that it changes people with LFS’s metabolism, which could link its anti-diabetes and cancer risk-reducing effects, but we still don’t know whether it can help people with LFS over the long-term – or even exactly why or how it works.
In fact, unlike most other cancer drugs, metformin has hardly changed for more than 100 years. It’s a lab-made version of chemicals found in a herb called goat’s rue, or galega. In medieval times, the plant was used to treat snake bites and plague.
It’s only recently, as they’ve learned more about how cancer starts, that scientists realised metformin might help reduce people’s cancer risk. MILI will test that theory over at least five years.
“Metformin wasn’t custom-made as an anti-cancer or even an anti-diabetes drug,” explains Blagden. “So there’s lots of questions about how it could work. There’s huge interest in it as a way of preventing cancer, but until we solve these questions, we can’t really put our hands on our hearts and say that we understand it. Once we do, though, we can come back with a better version.”
Precision cancer prevention: a new type of trial
As well as testing metformin, MILI will bring together a database of scans and samples that can be used to find better ways of detecting early-stage cancer in people with LFS and inform the use of risk-reducing mastectomies. By looking more closely at how these cancers start, researchers may even be able to find other ways to intercept them.
But the trial won’t just be for people with LFS. Those taking part will also be helping researchers learn about cancer in the general population.
We know TP53, the gene that is changed in LFS, is vital to preventing cancer. One of its discoverers – our former chief scientist, Professor Sir David Lane – even named it “the guardian of the genome”.
It’s still guarding some of its own secrets, too.
In people without LFS, changes to TP53 usually happen alongside multiple other changes in cancer cells. That makes it difficult for researchers to tell exactly what TP53 mutations do to help cancers grow or change how they act. By closely monitoring people with LFS, researchers should be able to pick out the other changes TP53 mutations make possible.
That monitoring is dependent on NHS-funded MRI scans. Without the George Pantziarka TP53 Trust, Professor Blagden wouldn’t have known how difficult it can be for people with LFS to get them. That problem needs solving. But, as Steph would say, the problems we know about are the ones we can fix.
That’s not the only way the LFS community has helped make MILI possible. Through the George Pantziarka TP53 Trust, people with LFS have helped plan and prepare the trial, and even raised funds to help pay for participants’ travel.
“This study has changed how we run clinical trials,” says Blagden. “We’ve decided to knit all of this into our unit’s DNA – to make sure that our priorities are always aligned with those of the people we’re working with.”
Where hope takes us
Blagden has worked particularly closely with Steph and Ava.
As part of a new TP53-focused buddying scheme, Steph has been paired up with Dr Miriam Dixon-Zegeye, one of Blagden’s PhD students.
It’s given Steph new understanding, and Miriam more motivation. “It’s tough to turn up in a lab every day and keep going – to try this, which doesn’t work, and try that, which doesn’t work – when you don’t have that human side in front of you,” says Steph. “Now Miriam can say, I know who I’m doing this for.”
Ava even joined Blagden for work experience. As part of that, she adapted information about MILI for Instagram, making the trial more visible to younger people with LFS.
The hope MILI offers means much more when it’s Ava who’s sharing it.
“Particularly when it comes to childhood cancer awareness, there is nothing more powerful in my view than saying, ‘Look at these people that are out there to help you,’” says Steph. “Ava’s seeing what the future of cancer prevention and treatment could look like.”
And Ava wants to become an oncologist. Like so many others in the LFS community, she wants to help, too.
Tim
