Woman at high risk of cancer becomes first in the world to trial drug which could reduce risk

  • ITV News Meridian's Penny Silvester spoke to Abbi about the five-year trial

A woman from Oxfordshire, diagnosed with a rare genetic condition which raises her chances of developing cancer, has become the first person in the world to trial a drug which could reduce the risk.

Abbi Ritson, 21, from Didcot, has Li Fraumeni Syndrome (LFS) which is caused by a mutation in a gene called TP53 - the most important anticancer gene in the body.

Researchers at the University of Oxford are investigating the use of a drug called Metformin as a way of reducing the cancer risk in people with LFS.

Abbi says it is giving her "hope for the future" and could make a difference to thousands of others.

"It gives people like me hope for the future because obviously we have lots of checks and things, have to go to the hospital quite regularly, and it will hopefully mean that if it works, then there's a chance we could be taking this drug and it could make a difference", Abbi said.

"It is a worry, I think, for all of us but it's something that we are very positive about and the fact that we get checked regularly and there's always doctors on the end of the phone if we have any worries, is really positive."

Abbi's family have all been diagnosed with Li Fraumeni Syndrome. Credit: ITV News Meridian

Abbi's family have all been diagnosed with LFS. Abbi's younger sister Ella died from a brain tumour at five years old.

At the time, the family did not know they carried the faulty gene.

Abbi's brother Harry had a brain tumour removed when he was 12 and her father is currently being treated for prostate cancer - his third bout of the disease.

Kevin Ritson, Abbi's father, said: "When I was diagnosed with the cancer, it was a shock, it's a big thing to take on obviously after losing Ella and Harry having his brain tumour.

"But we're being monitored all the time and if we weren't being monitored and we weren't having the checks, then they wouldn't have picked it up.

"I'm proud of all the kids, obviously for Abbi to be the first one to sign up to the trial and to be making a difference in life is amazing."

Abbi's younger sister Ella died from a brain tumour at five years old. Credit: Family handout

Professor Sarah Blagden, who is leading the research team at the Department for Experimental Oncology, University of Oxford, said: "The next steps for us will be to try and seek approval so Metformin can be licenced for use in patients with Li Fraumeni Syndrome.

"It's going to tell us a lot about the biology of why this treatment works and how cancer even forms in people with this condition and those are really important bits of information we've never yet been able to answer.

"The drug Metformin is already used extensively in treating diabetes and in another condition called Polycystic Ovary Syndrome but what we'd like to do is extend its use as a cancer preventative in people at particularly high risk of the disease.

"The trial will take about five years to run, we'll expect to have results around about 2027 but after that we'd like to take things forward so it is licenced for use in patients with Li Fraumeni Syndrome.

"This is literally just the beginning and we're planning to rollout a number of other cancer preventative studies in the future."

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What is Li Fraumeni Syndrome or LFS?

Li Fraumeni Syndrome (LFS) is a rare genetic condition that predisposes people to develop one or more cancers.

It is caused by a mutation in a gene called TP53, either inherited from a parent or occurring as a new mutation at conception.

TP53 is the most important anticancer gene in the body – its job is to stop cells becoming cancerous after they become damaged or stressed.

For most people with cancer the gene is only mutated in their cancer cells but, for people with LFS, it is mutated in all the cells in the body.

This means there is a very high risk of developing cancer for people with LFS – a lifetime risk of 90% for women, and about 70% for men.

Many people with LFS develop multiple cancers over their lifetimes.

Cancers associated with LFS include rare bone and soft tissue sarcomas, childhood brain tumours and leukaemias, but also more common cancers such as breast cancer.

What is the MILI trial?

The Metformin in Li Fraumeni (MILI) trial is a clinical trial investigating the use of a drug called Metformin as a way of reducing the cancer risk in people with Li Fraumeni Syndrome (LFS).

Metformin is a well-known and safe drug used to treat diabetes.

Laboratory experiments have shown that, in mice with LFS, Metformin can reduce the risk of them developing cancer.

This is because Metformin alters the metabolism of cells with mutated TP53 and makes them act more like normal cells.

A small study was carried out in people with LFS which showed that Metformin treatment caused the same kind of cellular changes that had been seen in the treated mice.

However, this is not enough to conclude that Metformin will reduce the risks of cancer in people with LFS.

For that, a larger clinical trial is needed – involving more patients and a much longer duration of treatment.

The MILI trial aims to enrol 224 patients with LFS in the UK, a large fraction of the approximate 600 people with it in the country.

In order to get the numbers of patients needed to address more detailed questions, such as whether Metformin is better at preventing certain types of cancer than others, the trial will be run in US, Canada, as well as the UK and the results will be pooled together.

Altogether it is expected that around 600 LFS patients from around the world will be included.

Half the people on the trials will take Metformin every day for up to five years and the other half will not – all participants will have regular check-ups for cancer, including whole-body MRI.

Five years has been estimated as long enough to give an early indication of whether differences in cancer incidence are due to treatment rather than being random (i.e. chance events) although longer follow-up may be implemented in the future.