Targeted expression of the Epidermal growth factor receptor in the respiratory system of Drosophila melanogaster to develop a lung cancer model

Cancer is one of the leading causes of death worldwide. Delayed diagnosis and lack of effective therapeutic approaches are the main reasons for this. This situation demands more functional strategies in drug development research. In this thesis, the respiratory system of the genetically modified Drosophila melanogaster was used to develop specific lung cancer models. Mutations in the EGFR pathway are one of the most frequent inducers of Lung cancer, especially in non-small cell lung cancer (NSCLC). In this study, the targeted expression of the constitutively active EGFR (EGFRCA) in the tracheal system of Drosophila was performed. Ectopic expression of EGFRCA throughout the airway system induced phenotypes with severe consequences such as airway malformations, epithelial thickening and hyperplasia, which often led to death in the early larval stage. On the other hand, the targeted expression of EGFRCA in Inka cells, ecdysis-triggering hormone (ETH) producing cells in the trachea, did not show any significant phenotypes in the larval stage. But in the pupal stage, it led to 100% lethality. The cellular level analysis of the pupal trachea displayed possible tumour-like morphological changes like severe regional hyperplasia and hypertropia and thickened epithelium at the branching points of the primary branches in dorsal trunks, where Inka cells are located. The complete lethality in the pupal stage points towards the disfunction of Inka cells, where the ETH production, and thereby the eclosion hormone (EH) secretion, is drastically suppressed or even terminated. It points out that the EGFRCA-induced changes in these cells interfere substantially with their normal role during the process of pupation. As the phenotypes observed in both driver lines are highly significant and easily monitorable, they can be efficiently used for drug-screening approaches and drug-resistance experiments.


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