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DOI: 10.1055/s-0036-1584607
Ectopic activation of EGFR signaling in the airway epithelium of Drosophila induces lung cancer-like phenotypes
Lung cancer is one of the most aggressive types of cancer with an extremely high overall fatality rate due to late state detection and the lack of late state treatment options. Drosophila is a model for studying chronic inflammatory diseases of the lung, it's tracheal system shares comprehensive structural and functional similarities with the human lung, thus making it an ideal model for studying the molecular framework underlying lung cancer development.
Targeted overexpression of human oncogenes and their Drosophila homologs in the airway epithelium was chosen to induce cancer-like phenotypes in Drosophila. The larvae were analyzed regarding hyper- and metaplasia of the epithelium. For this, we measured e.g. thickening of the epithelium or a change in number and size of the nuclei. Larvae showing a strong cancer-like phenotype were selected for treatment with potential anti-cancer drugs in a 96-well format.
A number of oncogenes were able to induce epithelial meta- and hyperplasia indicating that they can induce tumor formation in the airway system. A thickening of the epithelium and an increased number of nuclei are showing the proliferating state of the tissue. Ectopic overexpression of a constitutively active version of the EGFR gene in larval airway epithelia is lethal in early developmental stages. When treated with specific EGFR inhibitors these larvae can successfully develop into adult flies.
The results highlight the potential of Drosophila as a model in cancer research and its usefulness in high-throughput anti-cancer drug screenings. It is our goal to use Drosophila lung cancer models to understand the molecular underlying tumor formation and progression and to identify compounds that can be used as therapeutic agents.