Bedeutung einer K-RAS-Mutation für die Strahlensensibilisierung nach EGFR-Blockade

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Based on the results of the first funding period, which were concentrated on the role of K-Ras mutation on radiosensitization of human tumor cells after EGR inhibition, the project planned for the prolongation period will be focused on the role of the expression profile of mutated and wild-type Ras isoforms (K-Ras, H-Ras, NRas) for erbB-mediated radioresistance as well as Cetuximab resistance of head and neck squamous-cell carcinoma cells in vitro. The project will clarify the role of K-, H-, and N-Ras as biomarkers for radioresistance mediated by activation of erbB receptor-dependent signaling cascades, i.e. PI3K-Akt and Raf-MAPK-Erk. With respect to newest results concerning the role of the cellular microenvironment in vitro analyses will be performed under 2D- and 3D-cell culture conditions. The differential results concerning in vitro and in vivo radiation sensitivity of specific HNSCC cell lines after EGFR inhibition, which were obtained in the first funding period, the cell and molecular biological background will be investigated based on gene expression studies. Moreover, in the translational context the importance and radiobiological efficacy of EGFR targeting in combination with cisplatin-based radiochemotherapy will be studied in detail.