Lymphoma and Leukemia Cell Vulnerabilities and Resistance Identified by Compound Library Screens

Response to anticancer agents is often restricted to subsets of patients. Recognition of factors underlying this heterogeneity and identification of biomarkers associated with response to drugs would greatly improve the efficacy of drug treatment. Platforms that can comprehensively map cellular response to compounds in high-throughput provide a unique tool to identify associated biomarkers and provide hypotheses for mechanisms underlying variable response. Such screens can be performed on cell lines and short-term cultures of primary cells to take advantage of the respective models' strength, which include, e.g., the ability to silence genes or introduce somatic mutations to cell lines. Cohorts of patient samples represent the natural diversity of cancers, including rarer mutations and combinatorial patterns of mutations that are often absent from existing cell lines. We here summarize a simple and scalable method for the measurement of viability after drug exposure based on ATP measurements as a surrogate for viability, which we use to measure and understand drug response in cell lines and primary cells.