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Li-Fraumeni Syndrome

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This is the second time that a project led by Dr. David Malkin (The Hospital for Sick Children) has been awarded a Terry Fox New Frontiers grant. 

Renewed funding allows team to continue developing ways to detect and prevent tumours associated with Li-Fraumeni Syndrome

 

A team of Toronto- and Halifax-based scientists has received renewed funding from the Terry Fox Research Institute to continue its groundbreaking research into Li-Fraumeni Syndrome (LFS)—a rare disorder that causes almost all those affected to develop cancer at one point or another of their lives.

The project is led by Dr. David Malkin, a world-renowned researcher based out of The Hospital for Sick Children in Toronto. Dr. Malkin and his team hope to use the $4.95 million they will receive from the TFRI over the next five years to find new ways to improve outcomes for patients living with this devastating condition.

“There is currently no way to predict which individual with LFS will develop cancer, when that cancer might occur, or what types of cancer they will develop,” said Dr. Malkin. “Our goal is to learn enough about the disease to be able to accurately predict these things – and hopefully stop them before they happen.”

Today many cancers associated with LFS are frequently lethal by the time they are detected. Being able to know how and when tumours will form could increase chances of survival for people living with the disease, according to Dr. Malkin.

“Understanding how LFS works could open the door for the development and implementation of strategies that could prevent or significantly delay the onset of cancer for people living with this condition,” he said.

LFS is an inherited condition that affects around one in 2,000 to 5,000 people. It is usually passed on from parents to their children, and is caused by mutations in the TP53 gene, which ordinarily plays a significant role in suppressing tumour growth.

Because this gene is compromised in people with LFS, they have an increased risk of developing cancers. According to experts, 75 per cent of males and a whopping 93 per cent of females living with Li-Fraumeni develop cancer in their lifetimes. Forty per cent of people who carry a mutated TP53 gene develop cancers before the age of 25, and multiple cancers occur in at least 30 per cent of patients.

“Today, people living with LFS have no idea if and when something bad might happen to them or someone else in their family,” Dr. Malkin said. “We want to change that.”

To achieve this goal, Dr. Malkin and his team have used previous TFRI funding to analyse the effectiveness of the Toronto Protocol—a now internationally-adopted surveillance protocol that increases the chances of early cancer detection in people with LFS, significantly improving patient outcomes. They have also used TFRI funding to understand the molecular architecture of the disease and to develop mice and zebrafish models that will allow them to test for drugs that could help prevent or slow down development of the tumours in people with LFS.

With their new grant, the team hopes to start testing drugs, while simultaneously creating a mathematical model that will help predict at what age – and in what organs – tumours will develop.   

“New funding from the TFRI is allowing us to do this because it helps us take a major problem and come at it from four or five very different directions,” says Dr. Malkin. “We’ve got human genetics and genomics, diagnostic imaging, cell biology, animal models, and computer science on one project – and that is an incredible breadth of scientific expertise working together to solve this devastating disease…and that’s so exciting!”

Project Title: The Terry Fox New Frontiers Program Project Grant in Early Tumour Detection and Prevention in Li-Fraumeni Syndrome 
Principal Investigators:  David Malkin, Andrea Doria, Anna Goldenberg, Adam Shlien, Ran Kafri, Anita Villani, Trevor Pugh, Gang Zheng
Duration: 2018-2023
Total Award: $4.95M

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