Lung cancer is a devastating disease and is the leading cause of cancer related death globally. Squamous cell lung cancer (SQC) accounts for around 25% of all lung cancer diagnoses. Better strategies for the early detection, prevention and treatment of lung cancer are urgently needed. Using a novel in vitro model of SOX2-driven early SQC I performed a screen using tool compounds and compounds in late phase clinical development for potential efficacy in chemoprevention. I combined this approach with targeted genetic ablation studies to identify/characterise targets that may be key to the progression of SOX2-driven squamous cell carcinomas. In particular I highlight an AKT isoform dependence in SQC that could be exploited in future clinical chemoprevention studies.