Establishment of a drug sensitivity panel using human lung cancer cell lines

We established a drug sensitivity panel consisting of 24 human lung cancer cell lines. Using this panel, we evaluated 26 anti-cancer agents: three alk ylators, three platinum compounds, four antimetabolites, one topoisomerase I inhibitor, five topoisomerase II inhibitors, seven antimitotic agents and three tyrosine kinase inhibitors. This panel showed the following: a) Drug sensitivity patterns reflected their clinically-established patterns of ac tion. For example, doxorubicin and etoposide were shown to be active agains t small cell lung cancer cell lines and mitomycin-C and 5-fluorouracil were active against non-small cell lung cancer cell lines, in agreement with cl inical data. b) Correlation analysis of the mean graphs derived from the lo garithm of IC50 values of the drugs gave insight into the mechanism of each drug's action. Thus, two drug combinations with reverse or no correlation, such as the combination of cisplatin and vinorelbine, might be good candid ates for the ideal two drug combination in the treatment of lung cancer, as is being confirmed in clinical trials. c) Using cluster analysis of the ce ll lines in the panel with their drug sensitivity patterns, we could classi fy the cell lines into four groups depending on the drug sensitivity simila rity. This classification will be useful to elucidate the cellular mechanis m of action and drug resistance. Thus, our drug sensitivity panel will be h elpful to explore new drugs or to develop a new combination of anti-cancer agents for the treatment of lung cancer.