Resistance of rectal cancers to preoperative radio-chemo-therapy represents a major clinical problem. Thus far, neither biomarkers predicting response nor therapeutic targets for guided therapies could be established in al day clinical use. The aim of this study is to uncover mechanisms of radio resistance in colorectal tumor cells. Therefore radioresistant populations of two well established colorectal cancer cell lines (SW480 / SW 1463) are created by repetitive irradiation. Then, using RNAseq and DNAseq, expression-patterns and nucleotide sequences of these cells are determined. By comparing the resistant cell populations and their age matched controls we aim to identify genes / pathways mediating resistance . To explore the functional relevance of these genes / pathways they are deregulated using RNAi and cells are subsequently exposed to varying doses of irradiation.To unveil the molecular mechanisms of these genes mediating resistance, we plan to perform cell cycles analyses and analyze the DNA repair capacity.
DFG Programme
Research Fellowships
International Connection
USA
