Since EGFR acts upstream of both RAS and PI3K in lung tumorigenesis, here we explore the effect of disrupting the endogenous RAS-PI3K interaction in a mouse model of EGFR-driven NSCLC, showing that this interaction is required for both tumor onset and maintenance and providing proof of concept that targeting this interaction has potential for treating EGFR-mutant NSCLC, even though RAS genes are not mutated in this setting. The gene discussed is PIK3CA; the disease is neoplasm.