AN INFORMATION-INTENSIVE APPROACH TO THE MOLECULAR PHARMACOLOGY OF CANCER

Since 1990, the National Cancer institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines, The 5 0-percent growth-inhibitory concentration (GI(50)) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patter ns of 60 such GI(50) values encode unexpectedly rich, detailed informa tion on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many bill ions of distinguishable possibilities. These activity patterns are bei ng used in conjunction with molecular structural features of the teste d agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and mo dulators of activity in the 60 cell lines, For example, the informatio n is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. I t remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.