Analysis of Food and Drug Administration-approved anticancer agents in the NCI60 panel of human tumor cell lines.
Since the early 1990s the Developmental Therapeutics Program of the National Cancer Institute (NCI) has utilized a panel of 60 human tumor cell lines (NCI60) representing 9 tissue types to screen for potential new anticancer 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 the results of screening current Food and Drug Administration (FDA)-approved anticancer agents in the NCI60 screen, with an emphasis on those agents that target signal transduction. We analyzed results from agents with mechanisms of action presumed to be similar; we also carried out a hierarchical clustering of all of these agents. The addition of data from recently approved anticancer 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 website (http://dtp.cancer.gov/). The FDA-approved anticancer agents are themselves available from the NCI as a plated set of compounds for research use.
Holbeck
Susan L
SL
National Cancer Institute, Division of Cancer Treatment and Diagnosis, Developmental Therapeutics Program, Information Technology Branch, Bethesda, MD 20892, USA. holbecks@mail.nih.gov
Collins
Jerry M
JM
Doroshow
James H
JH
D000465:Algorithms; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017277:Drug Approval / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D054547:National Cancer Institute (U.S.); D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013810:Therapeutic Equivalency; D014015:Tissue Banks; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents