TORONTO, Canada—Cancer scientists led by Dr. John Dick at the Princess Margaret Cancer Centre have found a way to follow single tumor cells and observe their growth over time. By using special immune-deficient mice to propagate human colorectal cancer, they found that genetic mutations, regarded by many as the chief suspect driving cancer growth, are only one piece of the puzzle. The team discovered that biological factors and cell behavior—not only genes—drive tumor growth, contributing to therapy failure and relapse.
The findings, published today online ahead of print in Science, are “a major conceptual advance in understanding tumour growth and treatment response," said Dr. Dick, who holds a Canada Research Chair in stem cell biology and is a senior scientist at University Health Network’s McEwen Centre for Regenerative Medicine and Ontario Cancer Institute, the research arm of the Princess Margaret Cancer Centre. He is also a Professor in the Department of Molecular Genetics, University of Toronto. The research work was primarily carried out in Toronto by Antonija Kreso, Catherine O’Brien, and other members of the Dick lab with support from clinician-scientists at Mount Sinai Hospital and at the Ontario Institute for Cancer Research, and from genome scientists at St Jude Research Hospital, Memphis, and the University of Southern California, Los Angeles.
By tracking individual tumor cells, they found that not all cancer cells are equal: only some cancer cells are responsible for keeping the cancer growing. Within this small subset of propagating cancer cells, some kept the cancer growing for long time periods (up to 500 days of repeated tumor transplantation), while others were transient and stopped within 100 days. They also discovered a class of propagating cancer cells that could lie dormant before being activated. Importantly, the mutated cancer genes were identical for all of these different cell behaviors.
When chemotherapy was given to mice in which the human tumors were growing, the team made the unexpected finding that the long-term propagating cells were generally sensitive to treatment. Instead, the dormant cells were not killed by drug treatment and became activated, causing the tumour to grow again. The cancer cells that survived therapy had the same mutations as the sensitive cancer cells proving that cellular factors not linked to genetic mutation can be responsible for therapy failure.