Scientists identify treatment target that disrupts proteins’ interaction, offering hope for new therapeutic approach.
Scientists at City of Hope, one of the largest cancer research and treatment organizations in the United States, have discovered a new cellular mechanism that plays an important role in cancer cells’ ability to cause disease. The study will be published today (February 5) in
Advancement in Cancer Treatment
Blending laboratory experiments with computer simulations, Chen’s team created a powerful digital application of CRISPR gene-tiling technology to uncover potential cancer medicines that precisely target the β-propeller domain.
After identifying the chemical compound Cpd_AV2 as a strong candidate, the team applied this compound to human cancer cells in the laboratory. Integrin αV and β5 rapidly separated, dissolving communication between the two proteins and causing cellular death, effectively halting growth in cancer cell lines.
Clinically, the researchers found integrin αV overexpression in multiple cancer types, highlighting integrin αV’s lead role in cancer progression. High levels of integrin αV were also associated with a poor prognosis in 3,700 patients with cancers of the breast, pancreas, liver, lung, and brain.
Expanding Therapeutic Horizons
By expanding opportunities for developing targeted therapies that sever the connection between integrin αV and β5, the City of Hope-led findings suggest a potent new approach for cancer treatment and future medicine discovery studies.
“Our study showcases an innovative application of CRISPR gene-tiling technology, revealing previously undiscovered sites on proteins with the capacity to cause cancer,” said Chen, who is also division director of epigenetic and transcriptional engineering at Beckman Research Institute of City of Hope. “This breakthrough opens new avenues for the advancement of next-generation oncologic therapies, marking a significant milestone in City of Hope’s battle against cancer.”
Scientists estimate that up to 1,100 different proteins live on the DOI: 10.1038/s41594-024-01211-y
The research was partly supported by grants from the American Society of Hematology, Alex’s Lemonade Stand Foundation (18-11849), Stand Up To Cancer & Cancer Research UK (RT617) and the