Cancer-causing Protein “Turned Off”

It’s the most common cancer-causing protein, directly responsible for 30 per cent of all cancers and indirectly involved in virtually all cancers. For more 30 years, scientists have failed to target Ras, as the protein is known, but now researchers from U of T have  turned this protein off with an experimental drug.

“The inhibitors’ results were incredible,” said Michael Ohh, a professor in the Faculty of Medicine’s department of laboratory medicine and pathobiology. “We were shocked. Nothing has had the same effect.”

Normally, Ras promotes cell growth, but it can also cause uncontrolled growth when mutated or deregulated. As a result, this protein is involved in many forms of cancer and is mutated in over 90 per cent of pancreatic tumours – one of the deadliest forms of cancer.

The researchers discovered that another protein, called SHP2, turns Ras off.

“Our lab is known for another area of cancer biology,” Ohh explained. “But at the request of a colleague, we entered the Ras field about five years ago to study mutations in a rare form of childhood leukemia.”

Working with researchers from Indiana University and Toronto’s University Health Network, the team tested a SHP2 inhibitor on mice with glioblastoma, the most common and aggressive type of brain cancer. Remarkably, the inhibitor reduced these tumours by over 80 per cent.

“We were surprised to find that nobody had identified SHP2 as a switch that regulates Ras,” Ohh said.

Next, the team will work with a cancer surgeon at the University of North Carolina to treat mice that have human pancreatic tumours. If the SHP2 inhibitor is effective, the researchers will use this evidence to support human clinical trials.

“In addition to being a researcher, I’m also a gastroenterologist and I see a lot of patients with pancreatic cancer,” said Dr. Yoshihito Kano, co-author of the publication along with primary author Severa Bunda (who is, like Kano, a postdoctoral fellow). “These patients usually die within one year, even with chemotherapy, so this drug could potentially change lives.”

While their research is still in its early stages, Ohh and his team hope that their discovery will open up new perspectives in the field and potentially change cancer treatment.

“By understanding how this cancer-causing protein works, we hope to target it much more precisely than before,” said Ohh. “At the end of the day, we want other researchers to build on our fundamental discovery, providing more options for patients.”