An EGFR-Induced Drosophila Lung Tumor Model Identifies Alternative Combination Treatments

摘要: Lung cancer is the leading cause of cancer-associated mortality. Mutations in EGFR gene are among most important inducers lung tumor development, but success personalized therapies still limited because toxicity or developing resistances. We expressed constitutively active (EGFRCA) exclusively airway system Drosophila melanogaster and performed comprehensive phenotyping. Ectopic expression EGFRCA induced massive hyper- metaplasia, to early death. used lethal phenotype as a readout screened library FDA-approved compounds found that 1,000 compounds, only tyrosine kinase inhibitors (TKI) afatinib, gefitinib, ibrutinib rescued lethality whole-animal screening approach. Furthermore, we presence subtherapeutic afatinib dose identified bazedoxifene synergistically acting compound rescues EGFR-induced lethality. Our findings highlight potential Drosophila-based approaches not identify specific also discover act with known TKIs. Moreover, showed targeting together STAT-signaling promising strategy for treatment.