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From mini-guts to the Hippo Pathway: Shutting down tumour growth in colorectal cancer

This project has been completed

In order for cancer to grow inside our bodies, it must overcome a series of control mechanisms that are important for tissue growth. One mechanism which is responsible for body organ size is aptly called the “Hippo” pathway.

“This pathway constrains tissue size, and in cancer this pathway is inactivated, so the ability to control the growth of the tumour is lost,” says senior investigator Dr. Jeff Wrana, based at Toronto’s Lunenfeld-Tanenbaum Research Institute (LTRI) at Mount Sinai Hospital.

His newly-funded research team, which includes a handful of colleagues based at LTRI, will use their funding to understand how they can intervene and reactivate this pathway to suppress tumour growth.”

The team is focusing on colorectal cancer, the second leading cause of cancer death in Canada. Roughly one in every 14 people is likely to develop the disease.

“The Hippo Pathway, the same regenerative pathway that’s so critical in repairing the intestine, is also playing a key role in the initiation of colorectal cancers,” Dr. Wrana says. “So our first focus is on colorectal cancer, and how we can interfere with this pathway using small molecules.”

The team is divided into three sub-projects:

Project 1 members will focus on target identification – or identifying ways the Hippo pathway can be controlled;

Project 2 is aiming to identify small molecules and drug-like compounds that can act like inhibitors for the pathway;

Project 3 will create new therapeutics to treat colorectal cancer at different stages of disease.

Dr. Wrana says one of the things he’s most excited about is the cutting-edge technology the team will be utilizing. “Our core really is one of the top screening and mass spectrometry centres in the world,” he says. “We can exploit these technologies to do drug screens and do systematic mapping of protein networks and that kind of stuff, and then link it all back to colorectal cancer.”

Mini-guts, or little tissues derived from stem cells that look like the gut, will also be developed to test new therapeutics. Part of the project will create patient-derived mini guts to match each individual’s genetic background, taking personalized medicine to the next level.

“It’s an exciting aspect of modern science,” says Dr. Wrana. “We are absolutely elated to receive this grant, and we are so grateful to the Institute, and the critical role that donors play.”