SOME PRACTICAL CONSIDERATIONS AND APPLICATIONS OF THE NATIONAL-CANCER-INSTITUTE IN-VITRO ANTICANCER DRUG DISCOVERY SCREEN

During 1985-1990 the U.S. National Cancer Institute (NCl) phased out its murine leukemia P388 anticancer drug screening program and developed as the replacement a new in vitro primary screen based upon a diverse panel of human tumor cell lines. For each substance tested, the screen generates a remarkably reproducible and characteristic profile of differential in vitro cellular sensitivity, or lack thereof, across the 60 different cell lines comprising the panel. Several investigational approaches to display, analysis, and interpretation of such profiles and databases, derived from the testing of tens of thousands of substances during the past 4-5 years since the NCl screen became fully operational, have been explored. A variety of useful, practical applications of the in vitro screen have become apparent. As these applications continue to evolve, they are proving to be complementary to diverse other anticancer screening and drug discovery strategies being developed or pursued elsewhere. Reviewed herein are some practical considerations and selected specific examples, particularly illustrating research applications of the NCl screen that may be more broadly applicable to the search for new anticancer drug development leads with novel profiles of antitumor activity and/or mechanisms of action. (C) 1995 Wiley-Liss, Inc.