Examination of drug-adapted cancer cell lines as pre-clinical models of acquired resistance

Resistance formation to chemotherapy remains a major reason for the failure of cancer therapies.This project investigated the use of drug-adapted cancer cell lines as models of acquired resistance in cancer at different levels. Firstly, we investigated MALDI-ToF fingerprinting approaches in order to establish a reliable method for the authentication of cell lines of the same genetic origin. Indeed,the MALDI-ToF based spectra of a panel of parental neuroblastoma cell lines and their sub-lines adapted to a range of cytotoxic anti-cancer drugs resulted in promising results. However, the method needs to be further optimised to reliably authenticate all cell lines. For the understanding of the processes underlying resistance formation in cancer cell lines, it is essential to better understand the intra-cell line heterogeneity in parental cancer cell lines prior to resistance formation. The investigation of ten single cell derived clonal sub-lines of the Neuroblastoma cell line UKF-NB-3 by methods including chromosome painting and determination of drug resistance

profiles revealed a noticeable level of intra-cell line heterogeneity. Next, we established a

standardised drug adaptation assay that enables the comparison of the potential of a drug to induce resistance in a certain cancer cell line. Finally, we introduced and characterised a novel oxaliplatin adapted sub line of the neuroblastoma cell line SK-N-AS. Taken together, this project resulted in improved methods for use and investigation of drug adapted cancer cell lines as models of acquired drug resistance in cancer.