FURI | Fall 2020

Examining the Anti-Proliferative Properties of DUB Inhibitors in Primary Mesothelioma Cells

Mesothelioma is a rare and deadly cancer that typically consists of tumors in the pleural cavity of the lungs. A CRISPR/Cas-9 knockout screen was performed to study the effect of knocking out genes across the human genome on proliferation in malignant pleural mesothelioma (MPM) cells. Ubiquitin-Specific Proteases were found to have a significant effect on proliferation, which distinguished them as a drug target. AZD1775 is a pan-deubiquitinating enzyme inhibitor that has been shown to be effective in vivo for different cancers. This research demonstrates that AZD1775 is significantly anti-proliferative for primary MPM cells from both sarcomatoid and epithelioid subtypes.