Mining and visualizing large anticancer drug discovery databases.

In order to find more effective anticancer drugs, the U.S. National Cancer Institute (NCI) screens a large number of compounds in vitro against 60 human cancer cell lines from different organs of origin. About 70,000 compounds have been tested in the program since 1990, and each tested compound can be characterized by a vector (i.e., "fingerprint") of 60 anticancer activity, or -[log(GI50)], values. GI50 is the concentration required to inhibit cell growth by 50% compared with untreated controls. Although cell growth inhibitory activity for a single cell line is not very informative, activity patterns across the 60 cell lines can provide incisive information on the mechanisms of action of screened compounds and also on molecular targets and modulators of activity within the cancer cells. Various statistical and artificial intelligence methods, including principal component analysis, hierarchical cluster analysis, stepwise linear regression, multidimensional scaling, neural network modeling, and genetic function approximation, among others, can be used to analyze this large activity database. Mining the database can provide useful information: (a) for the development of anticancer drugs; (b) for a better understanding of the molecular pharmacology of cancer; and (c) for improvement of the drug discovery process.