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First publication of the PRISM method from 2016. 102 cell lines were labeled with unique 24-nucleotide barcodes and used to screen 8400 compounds. BRD-7880 was identified as a potent and highly specific inhibitor of aurora kinases B and C.
An updated panel of 578 barcoded cancer cell lines were used to profile the activity of 4518 existing drugs with a diversity of indications. An unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines. Results were used to begin the PRISM drug repurposing resource (depmap.org/repurposing).
Results from a standard PRISM assay using the PR1000 cell set showed INK4 overexpression (along with RB1 loss) to be among the top genomic alterations associated with resistance to CDK4/6 inhibition with Palbociclib. This paper also identified a new strategy to enhance inhibition of CDK4/6 kinases.
Results from a standard PRISM assay using the PR500 cell set suggested that the novel compound, XL177A, acts by USP7 inhibition and that sensitivity to USP7 inhibition is associated with the mutational status of TP53. This study also found two pediatric cancers, Ewing sarcoma, and malignant rhabdoid tumor, were sensitive to XL177A.
Collaborators in the Gray lab at Stanford developed INY-06-061, a potent and selective heterobifunctional degrader of ERK5 to be used as a tool for validating phenotypes associated with ERK5 ablation. Results from a standard PRISM assay using the PR800 cell set verified a lack of dependency on ERK5 expression for cell growth (as no cell lines were sensitive to INY-06-061 treatment).
This paper introduces a novel ‘nanoPRISM’ method that leverages the PRISM cell set to understand the structure-function relationship of nanoparticles. For this study, the PR500 was treated with a library of modular fluorescent nanoparticles to understand regulators of nanoparticle delivery. In particular, SLC46A3 (a lysosomal transporter) was identified as a negative regulator of lipid-based nanoparticle uptake.
This work details the creation of a first-generation metastasis map to reveal organ-specific patterns of metastasis of 500 PRISM cell lines. This was done by injecting pools of 5 cell lines into mouse xenograft models. Results were used to develop the MetMap resource (depmap.org/metmap).
The PR500 PRISM cell set was grown with either folic acid or 5-methyl tetrahydrofolate (THF) as a folate source and treated with several methotrexate doses. Cells exposed to 5-methyl THF were found to be more resistant to methotrexate indicating that environmental folate source affects folate metabolism and response to antifolate drugs.
A panel of 253 PRISM cell lines were cultured in 2D and 3D conditions for 15 days with chemotherapy treatment. 3D cultures retained >10% viability whereas 2D cultures fell to <0.1%. Overall this study showed that CDK9 inhibition enhances chemosensitivity in Myc-suppressed, chemo-persistent cells.
198 PRISM cell lines were pooled and profiled by scRNAseq with the 10X Genomics Chromium system. This work compiled the landscape of heterogeneity across cancer cell lines and identified recurrent programs of cellular heterogeneity shared between tumors and certain cell lines.
This work sought to create a comprehensive resource of the metabolic diversity of cancer. Part of the study involved pooling 544 adherent PRISM cell lines which were then grown under media conditions with varied amino acid concentration to understand the effect on cell viability.
This paper introduces the MIX-Seq method for multiplexed transcriptional profiling of pooled cell lines that undergo drug treatment. Individual cell line identities were determined based on their single-nucleotide polymorphism (SNP) profiles. This method enables profiling of chemical or genetic perturbation response in pools of 100+ cancer cell lines.
This study was focused on understanding the mechanism cells use to adapt to proteotoxic stress. Part of the work used a panel of 549 PRISM cell lines grown in either glucose or galactose (to increase dependency on mitochondrial metabolism) in the presence or absence of bortezomib. Increased mitochondrial metabolism promoted proteasome inhibitor resistance.
