Analysis of FDA-Approved Anti-Cancer Agents in the NCI60 Panel of Human Tumor Cell Lines

摘要

Since the early 1990's the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI) has utilized a panel of 60 human tumor cell lines representing 9 tissue types to screen for potential new anti-cancer agents. To date, about 100,000 compounds and 50,000 natural product extracts have been screened. Early in this program it was discovered that the pattern of growth inhibition in these cell lines was similar for compounds of similar mechanism. The development of the COMPARE algorithm provided a means by which investigators, starting with a compound of interest, could identify other compounds whose pattern of growth inhibition was similar. With extensive molecular characterization of these cell lines, COMPARE and other user-defined algorithms have been used to link patterns of molecular expression and drug sensitivity. We describe here results of screening current FDA-approved anti-cancer agents in the NCI60 screen, with an emphasis on those agents that target signal transduction. We have analyzed results from agents with mechanisms of action presumed to be similar; we have also performed hierarchical clustering of all of these agents. The addition of data from recently approved anti-cancer agents will increase the utility of the NCI60 databases to the cancer research community. These data are freely accessible to the public on the DTP web site (). The FDA-approved anti-cancer agents are themselves available from the NCI as a plated set of compounds for research use.