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 tumors – 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 tumors by over 80 percent.
“We were surprised to find that nobody had identified SHP2 as a switch that regulates Ras,” Ohh said.
The findings were recently published in Nature Communications.
Next, the team will work with a cancer surgeon at the University of North Carolina to treat mice that have human pancreatic tumors. If the SHP2 inhibitor is effective, the researchers will use this evidence to support human clinical trials.