It’s like a fire alarm in the cell
A Canadian researcher and entrepreneur translates fundamental discoveries in cancer epigenetics into new tools for earlier cancer detection and more effective treatment.
“If the genome is the book of life, DNA methylation acts like bookmarks,” explains Dr. Daniel De Carvalho, a senior scientist at the University Health Network’s Princess Margaret Cancer Centre in Toronto. “In cancer, these bookmarks get scrambled and produce a massive disruption of the epigenome.”
The epigenome determines which genes are active or silent in a given cell, and it explains why a skin cell produces other skin cells and not a liver cell. It is a complex layer of chemical tags and modifications on DNA and related proteins that control the expression of genes in cells. DNA methylation is the most common type of chemical tagging.
Dr. De Carvalho’s research focuses on understanding how cancer alters the epigenome and how these changes can be harnessed to improve cancer detection and treatment.
More than half of the genome consists of transposable elements, which are most often the result of past viral infections. In healthy cells, these ancient viral sequences are silenced. In cancer cells, because of the epigenetic disruption, these elements are reactivated. When that happens, the body reacts as if a real virus is present and triggers an immune response.
“It’s like a fire alarm in the cell,” says Dr. De Carvalho, who made this fundamental discovery and named the phenomenon viral mimicry in 2015.
Dr. De Carvalho and his team are currently translating this research into clinical tools to detect cancer formation at the earliest stages, monitor a patient’s response to treatment, and improve the effectiveness of cancer immunotherapies.
The DNA sequences of transposable elements exhibit a characteristic methylation pattern. Dr. De Carvalho and his team have developed a genome-wide method to profile DNA methylation from DNA collected from the blood.
This method can distinguish methylation patterns from those of a normal cell and a cancer cell. As a result, it can detect cancer earlier than a tissue test and measure the presence of disease following treatment and the response to therapy. The technology has been validated in two clinical trials and is being used in several hospitals.
To develop the technology for broad commercial use, Dr. De Carvalho founded a start-up company called Adela, which has so far raised more than $100 million US in financing.
Another application of Dr. De Carvalho’s research is the use of epigenetic drugs to induce viral mimicry in tumour cells in combination with immunotherapies. In this case, drugs are used to remove epigenetic markers, reactivating these ancient viral elements and triggering an immune response against the tumor. This approach has shown promise in treating lymphoma patients in a recent clinical trial.
“Fundamental discovery is what made me fall in love with science early in my career,” says Dr. De Carvalho. “At the same time, being able to work on the translational and technology development sides, taking those discoveries and turning them into tools or therapies that can help patients, makes the research especially meaningful.”
In 2025, Dr. De Carvalho was awarded the Peter Gilgan Canada Gairdner Momentum Award for his discovery of viral mimicry and for pioneering the development of a novel blood test for early cancer detection, classification and therapy monitoring.
At a glance
Issue
Cancer remains the leading cause of death in Canada. Unfortunately, many cancers are detected too late for effective treatment.
Research
A global leader in the field of cancer epigenetics, Dr. Daniel De Carvalho discovered that cancer cells trigger an immune response that he named viral mimicry. Dr. De Carvalho is leveraging this phenomenon to enhance the effectiveness of cancer immunotherapies. He is also developing tools to profile the DNA methylome of cell-free DNA and a blood test for early cancer detection and to monitor the response therapy.
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