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Targeting the Hippo Pathway to control tumour growth

In order to grow, cancers must overcome a series of mechanisms that control the normal functioning of our cells. One such mechanism is known as the “Hippo” pathway.

“The main job of this pathway is to control tissue size,” explains Dr. Jeff Wrana, a senior investigator at Toronto’s Lunenfeld-Tanenbaum Research Institute (LTRI) at Sinai Health. “When this pathway is working, tissue grows normally, but when there’s something wrong with it, tissue can grow uncontrollably, which is what happens in most cancers.”

Over the last four years, Dr. Wrana and his research team have received TFRI funding to study this pathway. It has allowed them to identify a number of key features that characterize it, including a potential vulnerability that, if exploited, could restore its normal functioning, stopping tumour growth.

“We have come to learn a great deal about this pathway. We now understand the inner workings of the Hippo system and are in a position to begin to identify and optimize therapeutics to shut it off,” says Dr. Wrana.

New objectives

As part of their new Terry Fox New Frontiers Program Project Grant (PPG), the team will receive $5.45M over the next six years to expand their Hippo Pathway studies, with the goal of moving their discoveries closer to the clinic.

In this iteration of the project, the team will move their energies away from colorectal cancer and focus on head and neck squamous cell cancer and triple-negative breast cancer. The team will also expand to include a drug development program that will seek to create treatments that target the pathway.  

“Our previous PPG provided key resources that allowed us to make exciting new findings that have the potential to really make a difference in the lives of patients,” says Dr. Wrana. “We’re very excited to continue to move ahead with these discoveries, and to integrate even more labs into our program, so we can maximize the impact of our work.”

“In this sense, the PPG provides a unique opportunity for us to do this because of the emphasis on integration of team members towards common objectives, which creates a real synergism that leads to transformative science.”

Building on past successes

This will be the second award to Dr. Wrana’s PPG team. Initial funding was provided for:

Under their first award, the team published a number of high-impact papers, including: