Researchers Deactivate Cancer-Causing Proteins

After 30 years of study by researchers around the world, a team of scientists at the University of Toronto in Canada, have developed an inhibitor drug for the cancer-causing protein, Ras. This protein is known to be directly responsible for approximately 30 percent of all types of cancers, and has been implicated in almost every other type of cancer known.

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

When functioning normally, the Ras protein encourages cell growth, but if the gene encoding the protein is damaged or mutated, it can lead to uncontrolled growth indicative of cancer. This protein is involved in a number of different cancers; in particular, the Ras gene is mutated in over 90 percent of tumors on the pancreas. Pancreatic cancer is one of the deadliest forms of the disease.

The team made a breakthrough when they discovered that an inhibitor protein – SHP2 – was able to deactivate Ras. “Our lab is known for another area of cancer biology,” said Ohh. “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.”

In collaboration with researchers from Toronto’s University Health Network and Indiana University, Ohh and his lab tested the effects of SHP2 on mice with a common, aggressive form of brain tumor known as glioblastoma.

The researchers found the inhibitor reduced tumor size by over 80 percent. “We were surprised to find that nobody had identified SHP2 as a switch that regulates Ras,” said Ohh.

The results of the study were published in the journal, Nature Communications. In continuation of the project, the researchers plan to work with a cancer surgeon at the University of North Carolina, and test the effectiveness of SHP2 on mice with human pancreatic tumors. If SHP2 proves effective at shrinking the pancreatic tumors, Ohh and his team will look into moving on to 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. “These patients usually die within one year, even with chemotherapy, so this drug could potentially change lives.”

Ohh and his colleagues are hopeful that their work will lead to new treatment options for patients with cancer. “By understanding how this cancer-causing protein works, we hope to target it much more precisely than before,” he said. “At the end of the day, we want other researchers to build on our fundamental discovery, providing more options for patients.”

Sources:

• University of Toronto Researchers “Turn Off” Cancer-Causing Proteins – http://www.dddmag.com/news/2015/12/university-toronto-researchers-turn-cancer-causing-proteins
• Bunda, S., Burrell, K., Heir, P., Zeng, L., Alamsahebpour, A., Kano, Y., Raught, B., Zhang, Z., Zadah, G., and Ohh, M. (2015). Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis. Nat Comm, 6 (8859).