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Metastatic Cancer

Understanding the differences between primary and metastatic tumours to save more lives

Even senior scientists can be surprised by new data - something Dr. Sean Egan experienced when he found out that breast cancer metastasis can be very different from their original primary tumour.

Dr. Egan and his TFRI PPG colleagues in Toronto are studying the similarities and differences between these primary and secondary tumours in several types of metastatic breast cancer and medulloblastoma, a common type of childhood brain cancer. A hundred Canadians are diagnosed with medulloblastoma each year.

“The biggest surprise was just how different metastatic disease seems to be. I would have expected them to be very similar, but in some cases there can be quite a difference,” says the senior scientist at The Hospital for Sick Children in Toronto.

Cancer is the second leading cause of death in Canada, killing around 76,000 people each year. Most of these deaths are caused by secondary tumours, or metastasis, that obstruct organ function and don’t respond to therapy. Yet most cancer treatment focuses on primary tumours, which is unlikely to cure the disease.

“The key is that these diseases can be different, and so we are trying to find ways to treat both compartments. The patient benefits would ultimately be if we could treat that disease with rational therapy,” says Dr. Egan.

The inspiration for their TFRI-funded project came from co-principal investigator Dr. Michael Taylor’s discovery and what he calls “revolutionary findings” that metastasis in brain tumours could be very different from the primary tumour. Dr. Egan and a few other colleagues had a shared interest in the findings with regard to their application to breast cancer.

The brain tumour metastases aren’t necessarily that similar to that of breast cancer, adds Dr. Egan, but Dr. Taylor’s approach can be easily applied. Further, some of the same signaling pathways are targeted by mutations in both cancer types, and the researchers could learn from each other's work with regards to the pathways involved.

By better understanding the relationship between the mutations that cause a primary tumour to form and the unique features of the metastatic tumour, more specific treatments can be devised – and more lives could potentially be saved.

“This is a team of four people, and everyone really brings something different and important into the mix,” said Dr. Egan. “We hope to revolutionize future therapy for patients.”

Project Title:The Terry Fox New Frontiers Program Project Killing the Hydra: Genetic dissection of actionable targets required for maintenance of metastatic disease

Duration: 2014-2019

Principal/Co Investigators: Sean Egan, Michael Taylor, Hospital for Sick Children, UofT; James Woodgett, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, UofT; Eldad Zacksenhaus, Toronto General Research Institute, UofT

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