From Flies to Therapy: A 20-Year Journey Leading to Cancer Clinical Trials

Scientists at the University of Montreal and its Institute for Research in Immunology and Cancer have taken a significant step forward in cancer treatment by initiating a phase-1 clinical trial for a novel small-molecule therapy targeting solid tumors. This breakthrough stems from over two decades of foundational research beginning with studies on the RAF protein in fruit flies. The RAF protein is part of the Ras-MAPK signaling pathway, which is often implicated in tumor development.

The collaborative effort between IRIC's drug discovery team, led by chemistry professor Anne Marinier, and intracellular signaling expert Marc Therrien, has culminated in developing a molecule that inhibits RAF dimerization—a process essential for its activation. Their pioneering work first identified the mechanism of RAF activation in Drosophila in the late 2000s, inspiring efforts to create inhibitors blocking this process.

This research journey involved creating biosensors to monitor RAF activity, developing multiple generations of candidate molecules, and testing their efficacy in vivo in mice. Funding from various sources, including the Strategic Collaboration Program and philanthropic contributions, supported these milestones.

In recent years, partnership with pharmaceutical companies like Ipsen has facilitated the optimization of these compounds, leading to the selection of a promising candidate for clinical testing. The recent approval by the U.S. Food and Drug Administration to commence clinical trials marks a historic achievement in translating basic research into potential therapies.

The development process included extensive synthesis and biological testing, involving over 1,850 molecules across different stages to refine a candidate that meets key pharmacological criteria. The ultimate goal is to offer a new treatment option for patients with solid tumors and contribute meaningful progress in cancer care.

This long-term endeavor exemplifies the critical importance of sustained research and collaboration in transforming scientific discoveries into life-saving medicines. The team remains hopeful that their molecule will eventually lead to a tangible clinical benefit, improving patient outcomes worldwide.