Researchers funded by The Terry Fox Research Institute have demonstrated that by analyzing patients’ blood samples, they are able to detect cancer earlier in individuals with Li-Fraumeni syndrome, an inherited condition with an almost 100 percent lifetime risk of developing cancer.
The research, led by Drs. Trevor Pugh and Raymond Kim at Princess Margaret Cancer Centre, University Health Network (UHN) and the Ontario Institute for Cancer Research (OICR) and Dr. David Malkin at The Hospital for Sick Children (SickKids), has been published in Cancer Discovery, and would not have been possible without the generosity of the patients who participated.
Li-Fraumeni syndrome is an inherited condition associated with a very high risk of developing cancer—often tumours affecting the breast, soft tissue, brain and other organs. It is caused by changes in the TP53 gene, which encodes a protein that helps to prevent tumour formation and is commonly termed the “guardian of the genome.”
Cancerous cells and healthy cells release pieces of DNA into the blood. By analyzing these DNA fragments, researchers are developing methods to detect whether a tumour has developed in the body. Testing blood samples for signs of cancer – often called liquid biopsies – is an attractive screening approach compared to imaging methods, which require specialized machines, and biopsies, which are more invasive.
The research team analyzed 170 blood samples from 82 individuals with Li-Fraumeni syndrome collected over several years, as well as 30 blood samples from individuals without Li-Fraumeni syndrome, providing a proof-of-principle framework that may support the detection of specific cancers earlier for individuals with Li-Fraumeni syndrome.
For Luana Locke and her family, early detection is invaluable and has prolonged her life many times already. Luana was diagnosed with breast cancer at age 25 and later discovered that her mother, children and many members of her extended family carried the same TP53 genetic change.
Luana, who has since had sarcoma, lung cancer, thyroid cancer and skin cancer, and her children have regular screenings, blood tests, MRIs of the entire body, and ultrasounds at Princess Margaret Cancer Centre and SickKids, to detect cancers early. After years of these scans Luana’s daughter, Juliet, was diagnosed with leukemia at age 14, a condition they have since learned may have been detected months earlier with this new blood sample analysis.
“Even though I have LFS, I never really felt cancer anxiety until after I was diagnosed,” says Juliet. “While my check-ups are reassuring, getting more precise diagnoses earlier is the next level in care.”
"Knowing that there is a high possibility that a cancer diagnosis can be detected at an earlier stage than the other surveillance tests goes a long way for the mental health of patients," says Chiquita Hessels, co-chair of the Li-Fraumeni Syndrome Association's Canada Chapter. "We have an incredibly talented and dedicated group with Drs. Trevor Pugh, David Malkin, Raymond Kim and their valued team members from across Canada who, with this potentially lifesaving discovery, can change the level of care not only for the rare syndrome groups in this study, but with all potential cancer patients in Canada and Internationally."
Dr. Malkin, leader of a longtime Terry Fox New Frontiers Program Project Grant studying the early detection and prevention of LFS in cancer, has been monitoring Luana’s children for almost 20 years, including her son who was one of the first people to follow a cancer surveillance protocol known as the “Toronto Protocol,” while Dr. Kim has been monitoring Luana for almost 10 years.
“Until now, the ways we did surveillance in children with cancer or in children with a genetic predisposition to cancer have been burdensome to families and the health care system – relying on multiple visits to the clinic, imaging tests and imprecise blood tests,” says Dr. David Malkin, staff oncologist, senior scientist and director of the Cancer Genetics Program at SickKids and a professor of paediatrics and medical biophysics at U of T. “Now, we can use a simple blood test to identify when, where and if a cancer is occurring. That is precision. These promising findings can be extended to all hereditary cancer syndromes to help improve the accuracy of cancer detection, especially for common tumour types, utilizing several analysis types that leverage different biological measurements.”
“For us, we’ve always known that early detection is the most important thing and so to add another layer of defence against that, another way to look for cancers and to find them sooner so you can begin treating them before they even have a chance to begin developing, is remarkable and gives us so much hope for ourselves and for others," says Luana. “We have so much to be thankful for and so much to be proud of in these amazing scientists and clinical practitioners that work within our system. And thank you to the Terry Fox Research Institute for funding them because it’s because of you and other agencies like you that this work can continue.”
“The Terry Fox Research Institute has been a long-time funder of this Li-Fraumeni research through our New Frontiers Program Project Grant and we know that families have wanted to see a test developed that could help with earlier detection and treatment for this disease, described as a ‘ticking time bomb’,” says TFRI President and Scientific Director Dr. Jim Woodgett. “We are delighted to see work under Terry Fox’s name that will enable clinicians to better diagnose and treat affected families as well as provide insight to other common cancers.”
The team will conduct a clinical trial to further test this approach and screen patients in the hope of finding their cancer earlier. These patients will include those with different types of high-risk cancer predisposition syndromes, including Li-Fraumeni syndrome, Lynch Syndrome, and Hereditary Breast and Ovarian Cancer; all of which are brought under a nation-wide research consortium that Drs. Pugh and Kim founded in 2017.
This work was supported by the Terry Fox Research Institute and Terry Fox Foundation, Canadian Institutes for Health Research, TD Ready Challenge, the McLaughlin Centre at the University of Toronto, Shar Foundation, FDC Foundation, Bhalwani Family Charitable Foundation, Karen Green and George Fischer Genomics and Genetics Fund, Lindy Green Family Foundation, The Devine/Sucharda Charitable Foundation, SickKids Foundation, The Garron Family Cancer Centre, The Princess Margaret Cancer Foundation and the Ontario Institute for Cancer Research. This work would not have been possible without the generosity of the patients who participated in this study.
This story was prepared based on a joint press release prepared by SickKids, PMCC, OICR and TFRI.