Informatics based on human cancer cell line-panel-its application to the discovery of molecular target-based drugs and the diagnosis of chemosensitivity

Abstract

Studies conducted at the US National Cancer Institute(NCI)and in our laboratory show that databases including the drug sensitivities of panels of many human cancer cell lines(cancer cell line-panel) provide valuable information on the molecular pharmacology of anticancer drugs. The cancer cell line-panel is a unique system where “a wet system (biological experiments)” and “a dry system (informatics)” are efficiently combined. Its characteristic is to predict the action mechanism of a testing compound. We have been using this system for drug discovery, coupled with various target-based drug screenings. We used the system to identify a novel DNA minorgroove binder, MS-247, which has inhibitory activity against topoisomerases I and II, and potent in vivo antitumor activity against various human cancer xenografts. We also discovered a potent novel telomerase inhibitor, FJ 5002, by mining our database with the COMPARE algorithm, followed by experimental validation. We investigated the gene expression profiles of the cell lines by using cDNA microarrays to find profiles determining cellular chemosensitivity and new targets for anticancer drugs. Our integrated database, including the chemosensitivities and gene expression profiles of the cell-line panel, could provide a basis for drug discovery and personalized therapy. © 2003, THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM. All rights reserved.