Our multiplexed cell viability platform, PRISM (profiling relative inhibition simultaneously in mixtures), enables screening of potential cancer therapeutics at an unprecedented scale. We routinely assess the effects of perturbations against more than 900 cancer cell lines concurrently through the use of unique oligonucleotide barcodes stably transduced into individual cancer cell lines. Following barcode transduction, individual cell lines are pooled together in groups of 20-25 based on growth rate similarity, then thawed into 384-well assay-ready plates containing compounds of interest. After 5 days of growth, isolated mRNA is used to detect transcribed barcode abundance of each individual cancer cell line to measure relative viability. We leverage the baseline cellular features (e.g., gene expression, cell lineage, mutation, copy number, metabolomics, proteomics, genome-wide RNAi and CRISPR dependencies) of each cell line to interpret viability profiles, enabling identification of drivers of differential sensitivity and potential biomarkers of compound response. Critically, the scale and throughput of PRISM has enabled the generation of large, publicly available datasets and the rapid characterization of emerging therapeutic targets and classes (e.g., isoform-selective RAS inhibitors and degraders). Although the read-out of PRISM is relative cell line viability, the platform can be used to answer a multitude of scientific questions. For example, PRISM data can be used to identify potential patient populations who would most benefit from treatment with a specific compound, uncover unexpected off-target toxicities, and validate mechanism of action hypotheses on a more holistic scale. Ultimately, PRISM offers a large-scale and comprehensive platform for the testing and validation of anti-cancer compounds to aid in the search for new oncology therapeutics. Citation Format: Ellen Nguyen, Shiker Nair, John Davis, Antonella Masciotti, Connor Mochi, John Finn, Cole Ponsi, Brienne Engel, Claudine Mapa, Mustafa Kocak, Melissa Ronan, Matthew G. Rees, Jennifer A. Roth. Identifying therapeutic mechanism of action and new potential patient populations using PRISM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2748.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.