Targeting Ubiquitin Signaling vulnerabilities in KEAP1-Inactivated Lung Cancer

Lung cancer cells rely on protein homeostasis regulators, especially within the ubiquitin-proteasome system (UPS), to sustain malignancy. Genetic alterations in UPS components, such as E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs), are common and create context-dependent therapeutic dependencies. We have investigated how these changes drive tumor formation, we conducted CRISPR screens on metabolically stressed murine lung cancer models and identified specific cancer vulnerabilities, including KEAP1.