Abstract

The heterogeneity and individuality of cancer diseases is tremendously high. Recent genomic investigations revealed a tremendous genetic complexity in the cells from solid cancer diseases. Cancer cell (sub)populations may differ substantially between primary tumours and metastases as well as within primary tumours. This heterogeneity is a consequence of cancer clonal evolution processes. Among other models, comprehensive cancer cell line collections will be required to address this wide complexity. Resistance acquisition to anti-cancer therapies represents a major obstacle to the development of effective anti-cancer therapies and contributes to cancer cell clonal evolution processes and heterogeneity. Major cancer cell drug resistance mechanisms have been discovered in drug-adapted cancer cell lines including the ABC transporters ABCB1 (also known as P-glycoprotein or MDR1 ) and ABCC1 (also known as MRP1 ) and clinically relevant resistance mechanisms to so-called “targeted therapeutics” (e.g. EGFR tyrosine kinase inhibitors, oncogenic BRAF inhibitors). The Resistant Cancer Cell Line (RCCL) collection (http://www.kent.ac.uk/stms/cmp/RCCL/RCCLabout.html) consists of approximately 1000 cell lines from 15 different cancer entities with acquired resistance to a broad range of cytotoxic and targeted anti-cancer drugs. I will present an overview of our current projects on the studying of drug-induced cancer cell resistance mechanisms, the investigation of anti-cancer agents, and the examination of drug-induced clonal evolution processes.