In vitro modelling of human tumour behaviour in drug discovery programmes

Human tumour cell lines have played an important part in our understanding of cancer and have been used extensively in the discovery and characterisation of new chemotherapeutic drugs. A potential weakness of such cell lines is that they may have lost important properties originally possessed in vivo, including potential targets for therapy. This review discusses how possible differences between tumour cells in cancer patients and cell lines might be identified by the use of short-term cultures of human tumour cells taken directly from cancer tissue, termed here primary cultures. Cell-cycle time is one important difference between tumours and cell lines and it is known that the cell-cycle times of primary cultures cover the same wide range as estimated in vivo cell-cycle times. Because tumour cells have at least two pathways to cell death, one from interphase and one from mitosis, changes in cell-cycle length can modify the balance of such pathways. Responses of primary cultures to DNA-damaging drugs and inhibitors of growth factor receptors also differ from those of cell lines, suggesting that the process of developing a cell line can result in the loss of important cellular responses. Without an appreciation of these changes our ability to discover new targets for the development of improved cancer therapy may be jeopardised. The identification of cell lines that preserve potential targets is an important goal in cancer biology and research using primary cultures will help in this identification.