ArticleGenome medicine2021
Deconvolution of cell type-specific drug responses in human tumor tissue with single-cell RNA-seq.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 96 citations in OpenAlex.
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- Decoding drug-responsive cell subpopulations in triple-negative breast cancer using single-cell multiomics.iScience · 2026Article
- scArchon: a scalable benchmarking framework for assessing single-cell perturbation models.Genome biology · 2026Article
- Systematic design of combination therapy by targeting master regulators of coexisting diffuse midline glioma cell states.Nature genetics · 2026Article
- Downregulation of SLC12A5 in glioblastoma multiforme: a novel prognostic biomarker associated with brain edema and radiomic features.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Dissociable perfusion chip (DPC): perfusable microfluidic chip for single-cell screening of anti-cancer drugs in live glioblastoma explants.Lab on a chip · 2026Article
- AGPAT3 reshapes tumor cell vulnerability to IFNγ-mediated ferroptosis and enhances immunotherapy efficacy through lipid remodeling.Journal for immunotherapy of cancer · 2026Article
- Primary glioma cell culture: from monolayer to organoids.Protoplasma · 2026Review
- Pharmacogenomic Synthetic Lethal Screens Reveal Hidden Vulnerabilities and New Therapeutic Approaches for Treatment of NF1-Associated Tumors.Molecular cancer therapeutics · 2026Article
- Benchmarking algorithms for generalizable single-cell perturbation response prediction.Nature methods · 2026Article
- An expanded role for single-cell chemical genomics profiling in drug discovery.The Biochemical journal · 2026Review
- Drug and single-cell gene expression integration identifies sensitive and resistant glioblastoma cell populations.Nature communications · 2026Article
- Squidiff: predicting cellular development and responses to perturbations using a diffusion model.Nature methods · 2026Article
- Shaping the future one slice at a time: How 3D organotypic tumour slice models are driving drug discovery in ovarian cancer.Translational oncology · 2026Review
- Toward functional precision oncology: organotypic brain slices in glioblastoma.Frontiers in oncology · 2026Review
- A novel TRP channel-related prognostic model of glioma based on transcriptomics and single cell sequencing analysis.Discover oncology · 2025Article
- The applications of single-cell multiomics in drug screening.Pharmaceutical science advances · 2025Review
- Glioportal: a comprehensive transcriptomic resource unveiling ligand-mediated mesenchymal transition in glioblastoma.Neuro-oncology · 2025Article
- Squidiff: Predicting cellular development and responses to perturbations using a diffusion model.bioRxiv : the preprint server for biology · 2025Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPreclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity.
methodsWe combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to drug perturbations on slices derived from six glioblastoma (GBM) resections to identify conserved drug responses and to one additional GBM resection to identify patient-specific responses.
resultsWe used scRNA-seq to demonstrate that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue and the feasibility of drug screening from an individual tumor. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients. Etoposide has a conserved impact on proliferating tumor cells, while panobinostat treatment affects both tumor and non-tumor populations, including unexpected effects on the immune microenvironment.
conclusionsAcute slice cultures recapitulate the major cellular and molecular features of GBM at the single-cell level. In combination with scRNA-seq, this approach enables cell type-specific analysis of sensitivity to multiple drugs in individual tumors. We anticipate that this approach will facilitate pre-clinical studies that identify effective therapies for solid tumors.
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