International team uses AI to discover new drugs for fighting cancer and infectious disease

A Western-led interdisciplinary research team is using artificial intelligence (AI) to target a potentially harmful enzyme found in the human body that, if left untreated, can cause cancer and infectious disease.

Biochemistry and computer science professor Pingzhao Hu and his Western team are investigating the negative impact of the stress response enzyme Pin1 and developing targeted therapeutics for the treatment of cancer and infectious diseases it can cause.

The Western team, which includes Schulich School of Medicine & Dentistry faculty Kun Ping Lu, Xiao Zhen Zhou and computer science professor Boyu Wang, are working in collaboration with international researchers, Jonathan Weitzman of Université Paris Cité and Olivier Sperandio of the Pasteur Institute.

It was announced today their collaborative project, Pin-AI, received four years of federal funding. "Canadian and French researchers, combining our expertise in AI, computational biology and cancer biology, will jointly design new AI algorithms to discover new Pin1 inhibitors and we will test our findings in both human and model systems across labs in both countries," said Hu, Canada Research Chair in Computational Approaches to Health Research.

"Over the four-year project, our teams will also exchange visits with researchers and students, collaborating closely to advance this AI-driven approach to develop targeted cancer and infectious disease therapeutics."

For the project, Hu and Wang, in collaboration with Sperandio, will lead efforts to create an AI model able to quickly analyze more than 100 million compounds in chemical libraries to identify potential drugs that can block Pin1.

Using these advanced AI techniques, Lu, Zhou and their French research partners will study the Pin1 enzyme in humans and parasites to design new drugs that specifically target Pin1 in cancer for both humans and cattle. They will test the most promising of these drug candidates on human triple-negative breast cancer cells (an aggressive type of invasive breast cancer that has fewer treatment options) to see how they affect cancer growth and spread. Meanwhile, Weitzman will test these compounds in cattle with cancer caused by infectious parasitic agents, building on their previous collaborative work showing parasites secrete Pin1 to drive cancer development.

"We now understand AI can do far more than just screen existing compounds. It can actually design and guide the synthesis of entirely new ones. With these capabilities, AI can generate entirely new chemicals capable of inhibiting Pin1 with unprecedented precision," said Zhou, a pathology and laboratory medicine professor at the Schulich School of Medicine & Dentistry. "In short, AI doesn't just find potential drugs. It actively shows us how to create them."

Lu and Zhou made the groundbreaking discovery of Pin1 in 1996, a finding described in a landmark Nature paper. Pin1 is a specific protein in cells that becomes active or changes its behavior in response to stressors, like environmental challenges, toxins or physiological changes.

"Our team has already demonstrated strong results in animal models, and we are now planning clinical trials using existing drugs to target Pin1 for cancer treatment, highlighting the potential for a fundamental shift in cancer therapy. By targeting this pathway, driven by AI, we can use immunotherapy for previously unresponsive tumors, giving patients a real chance to see their tumors shrink and even disappear," said Lu, Western Research Chair in Biotherapeutics and biochemistry professor at Schulich School of Medicine & Dentistry.

Provided by University of Western Ontario