Integrating the NCI‐60 Data with “Omics” for Drug Discovery

Abstract

Abstract Preclinical Research The National Cancer Institute (NCI)‐60 screening panel represents one of the largest chemical cell line screening endeavors ever undertaken. This screen, starting in the early 1990s, has evaluated the effect of ∼400,000 compounds on the growth of a panel of over 60 human cancer cell lines. The screen and the extensive characterization of the cell lines provide a wealth of data on determinants of drug sensitivity, much of it publicly available. Here, an overview of the data is provided including basic characteristics of cell lines, the variance of 50% growth inhibitory concentration of over 40,000 chemicals, and expression of 17,775 genes across these cell lines. This analysis revealed that only a fraction of compounds have differential sensitivities across lines. For the majority of compounds, the genomic underpinnings of drug sensitivity cannot possibly be discerned from the data as there is no significant variance between cell lines. This limitation applies, surprisingly, to platinum agents and even to tamoxifen, demonstrating the limitation of this screening methodology to capture all differences that predict drug sensitivity in the context of human cancer. In contrast, methotrexate has remarkably disparate effects across cell lines, suggesting that the origin of its sensitivity can be discerned. Correlations of drug sensitivity and gene expression reveal some remarkably robust correlations across the NCI‐60 cell lines, suggesting their value as predictive biomarkers, or perhaps even drug targets. These results demonstrate both the power and limitations of NCI‐60 type screens to identify the determinants of drug sensitivity.