Media Releases

U of T researchers ‘turn off’ most notorious cancer-causing protein

December 1, 2015

TORONTO, ON — It’s known as the most com­mon can­cer-caus­ing pro­tein, direct­ly respon­si­ble for 30 per cent of all can­cers and indi­rect­ly involved in vir­tu­al­ly all can­cers. For over 30 years, sci­en­tists have failed to suc­cess­ful­ly tar­get it, but now researchers from U of T can turn this pro­tein off with an exper­i­men­tal drug.

“For sev­er­al decades, sci­en­tists have tried to turn off a pro­tein called Ras,” said Michael Ohh, a pro­fes­sor in the Fac­ul­ty of Medicine’s Depart­ment of Lab­o­ra­to­ry Med­i­cine and Patho­bi­ol­o­gy. “But despite their efforts, we ulti­mate­ly haven’t seen much progress. In fact, it’s been coined the ‘undrug­gable’ pro­tein.”

Dr. Yoshihito Kano (left) and Professor Michael Ohh

Dr. Yoshi­hi­to Kano (left) and Pro­fes­sor Michael Ohh

Nor­mal­ly, Ras pro­motes cell growth, but it can also cause uncon­trolled cell growth when mutat­ed or dereg­u­lat­ed. As a result, this pro­tein is a key play­er 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. But on the request from a col­league, we entered the Ras field about five years ago to study muta­tions in a rare form of child­hood leukemia,” said Ohh. “We were sur­prised to find that nobody had iden­ti­fied SHP2 as a switch that reg­u­lates Ras that it could be tar­get­ed.”


Mouse tumour

Mouse tumour

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.

“The inhibitors’ results were incred­i­ble — we were shocked,” said Ohh. “Noth­ing has had the same effect.”

The researchers’ 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 tumours. If the SHP2 inhibitor is effec­tive, the

researchers will use this evi­dence to sup­port future 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 Yoshi­hi­to Kano, co-author of the pub­li­ca­tion along with Sev­era Bun­da, the pri­ma­ry author. “These patients usu­al­ly die with­in one year, even with chemother­a­py, so this drug could poten­tial­ly change my patients’ 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 bet­ter 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.”


Pub­li­ca­tion link:

Katie Bab­cock
Com­mu­ni­ca­tions Offi­cer
Depart­ment of Lab­o­ra­to­ry Med­i­cine and Patho­bi­ol­o­gy, Uni­ver­si­ty of Toron­to
Tel: 416–278-6568