Abstract
Abstract MYC and hypoxia gene clusters are two most commonly recurring transcriptional programs in a heterogenous tumor. Understanding the cellular fitness of MYC-driven cancer cells in normoxia and hypoxia may lead to identification of cancer cell vulnerabilities. Using genome-wide CRISPR screenings of MYC-driven liver cancer cells cultured in 21% and 1% oxygen in monolayer, and 21% oxygen in 3D spheroid over 4 weeks, we not only identify many targetable essential genes under all three conditions but also context-specific fitness genes and pathways. In parallel, we perform drug screening under three conditions. We find that cells respond to 125 FDA approved oncology drugs in different ways in normoxia, hypoxia and 3D. Our resource study highlights unique epigenetic and metabolic dependency of MYC-driven cancer cells in different tumor environments. Citation Format: Jun Yang. Cellular fitness of MYC-driven cancer cells to genetic and pharmacologic perturbations in normoxia, hypoxia and 3D culture [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A167.
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