Cancer is the 2nd most frequent cause of death in the industrialised world. Despite substantial improvements over the last decades, the prognosis remains unacceptably poor for a significant fraction of cancer patients. Particularly, the situation remains grim for patients suffering from the metastasised disease. Therefore, effective systemic therapies are needed to improve therapy outcomes.
The occurrence of drug resistance is a major obstacle to successful anti-cancer therapies. Many cancers respond initially well to therapy but eventually, cancer recurs as a drug-resistant disease resulting in patient death. Over the last years, it has become clear that cancer diseases are characterised by a tremendous inter- and intra-tumour heterogeneity. Due to their mutator phenotype cancer cells are subject to continuous clonal evolution processes resulting in tumours that consist of countless numbers of different (sub)species. Even (sub)species from the same tumour family may require different therapies.
Anti-cancer therapies exert an additional selective pressure on cancer cell populations further affecting the clonal evolution processes eventually resulting in resistance acquisition. These processes cannot be studied by the analysis of tumour tissue samples alone. Serial tumour biopsies would be required but these are difficult to obtain because they are invasive and stress the patient in the absence of a personal benefit. Moreover, they may not be representative due to the intra-tumour heterogeneity. Therefore, model systems are needed to investigate the mechanisms underlying drug resistance acquisition in cancer cells in order to develop hypotheses that can be tested by the use of the clinical material.
We have established a collection of drug-resistant cancer cell lines from different cancer entities and are currently approaching the number of a 1000 resistant cancer cell lines. The lists of cell lines can be found below. The effort has started at the end of the 1980s in the laboratory of Jindrich Cinatl in Frankfurt am Main, Germany. Martin Michaelis has been involved in the development for more than a decade as a member of Jindrich Cinatl’s laboratory. In the meantime, he has started his own group at the University of Kent and Jindrich Cinatl and Martin Michaelis continue their joint effort on the RCCL collection.
The drugs we use include all major classes of cytotoxic anti-cancer drugs as well as targeted agents. The cancer cell lines are continuously exposed to increasing anti-cancer drug concentrations. The aim is to establish readily growing sub-lines that show a clear resistance to the selection agent.
Thanks for support
Hilfe für krebskranke Kinder Frankfurt e.V.
Frankfurter Stiftung für krebskranke Kinder
The University of Kent
Deutsche Leukämie-Forschungshilfe (DLFH)
Dr Mildred Scheel Stiftung
Kent Cancer Trust
The Royal Society
Society of Biology