The low survival rates of three of the four most lethal cancers in North America – pancreatic, colorectal and lung – are associated with KRAS mutations, a well-established cancer driver. Although there is an urgent need for KRAS-targeting therapeutics, so far there has been a lack of clinically available drugs as oncogenic KRAS is very difficult to target directly.
Toronto Innovation Acceleration Partners (TIAP) announced today the launch of a new LAB150 project focusing on breakthroughs in novel cellular drug screening systems in oncology-focused scientific KRAS research by Professor Igor Stagljar at the University of Toronto, a TIAP Member.
This latest LAB150 project aims to develop therapeutics targeting the protein-protein interactions of KRAS and its downstream interacting partners. Recent therapeutic approaches are directed at the KRAS G12C mutation, but other common mutations, such as G12D and G12V, remain largely untargeted. The innovative approach undertaken by the Stagljar lab differs from current modifying approaches by targeting specific protein–protein interactions (PPIs) of KRAS and its downstream effectors. This is made possible through the use of two novel live cell high-throughput assays called the Mammalian Membrane Two-Hybrid Drug Screening (MaMTH-DS) and Split Intein Mediated Protein Ligation (SIMPL). Both assays were developed by Dr. Stagljar’s team, and one of them (MaMTH-DS) will soon be published at Nature Chemical Biology.
“I’m extremely happy that TIAP and Evotec recognized the power of our two recently developed innovative drug screening assays, MaMTH-DS and SIMPL, to identify PPI inhibitors of oncogenic KRAS mutants” says Dr. Stagljar. “ Since KRAS mutations represent the most common oncogenic alterations in all of human cancers, finding therapeutic approaches that target KRAS’s vital PPIs would have tremendous clinical impact for patients.”
This brings the total to six projects currently underway within the LAB150 program. LAB150 is a partnership between TIAP and Evotec SE with the goal of accelerating academic innovations towards commercial outcomes by not only providing capital but, equally important, ensuring expertise and drug discovery infrastructure on pharmaceutically validated platforms.
“The LAB150 program will help bring new discoveries and therapies from the lab into clinical development and validation. Dr. Stagljar’s research has tremendous potential to help treat several forms of cancer and improve patient outcomes” says Dr. Vivek Goel, Vice President of Research and Innovation at the University of Toronto.
“This project has the potential to transform outcomes for cancer patients that currently have limited options. Dr. Stagljar’s novel technologies paired with the drug discovery screening platforms of our partner Evotec SE, demonstrates the opportunity to translate novel science towards future therapies,” says Rafi Hofstein, President and CEO of TIAP. “With six projects funded and an extensive pipeline under evaluation, we have established LAB150 as a proven mechanism to efficiently select and advance front-runner health care research from our Members.”
