Cancer isn’t a single disease, nor are tumours made up of just one type of cell. Cancers are complex communities of diverse cells that can change over time, allowing them to adapt to new conditions, evade treatment, and survive. This ability to shift between different identities, known as cellular plasticity, is increasingly recognized as a key driver of cancer growth and treatment resistance.
With $3 million in funding from a Terry Fox New Frontiers Program Project Grant, a Toronto-based research team is tackling this challenge across three of the most aggressive and hard-to-treat cancers: glioblastoma, triple-negative breast cancer, and acute myeloid leukemia (AML). By investigating how stress and injury, including inflammation and changes in the tumour environment, influence cancer cell behaviour, the team aims to uncover new ways to make hard-to-treat cancers less adaptable and more vulnerable to treatment.
“By understanding how cancers adapt, our goal is to find new ways to block these processes, making cancer cells less flexible, more like normal cells, and easier to eliminate with treatment,” says Dr. Peter Dirks, senior scientist at the Hospital for Sick Children (SickKids) and the project’s lead. “Ultimately, this research could lead to better therapies and improved survival for people facing these difficult cancers.”
In glioblastoma, an aggressive form of brain cancer, the team will study how cancer cells shift between different cell types, particularly when the brain experiences injury or inflammation. They will then explore whether encouraging these cells to become more like normal brain cells could slow tumour growth and improve the cancer’s response to therapy.
For triple-negative breast cancer, a disease that is particularly aggressive in younger women, they will explore how inflammation and stress within body fat might influence cancer’s behaviour. By testing new ways of reducing this stress—including altering the type of fat or targeting the specific biological pathways involved—they hope to make these cancers easier to treat.
In acute myeloid leukemia, the team will study how the blood cancer’s stem cells survive under stress and withstand therapies. By targeting their survival mechanisms—including changing how genes are read and behave and forming protective structures—they aim to develop new treatments that prevent cancer cells from escaping and returning after therapy.
“Cell plasticity is a challenge that lies at the heart of many cancers. If we can pinpoint the mechanisms that allow cancers to adapt, resist treatment, and survive, we can identify new drug targets that could be relevant across many different cancer types,” says Dr. Dirks, who is also a professor of neurosurgery at the University of Toronto and Head of Neurosurgery at the Hospital for Sick Children.
“This work could pave the way for an entirely new class of drug therapies designed to make cancers less adaptable, more treatable, and ultimately improve outcomes and quality of life for people facing some of the most challenging cancer diagnoses.”