ArticleNature communications2021
Single-cell transcriptional changes associated with drug tolerance and response to combination therapies in cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
165 citing papers in PubMed, 1 synthesis or guideline pooled it, 264 citations in OpenAlex.
- Multilevel Mechanisms of Cancer Drug Resistance.International journal of molecular sciences · 2024Pooled it
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses.Molecular therapy. Oncology · 2026Article
- Data-centric feedback loops for next-generation immunotherapy development.Nature biomedical engineering · 2026Review
- Multiscale learning of gene network-driven phenotypic dynamics of single cells.Molecular systems biology · 2026Article
- Integrating single-cell and bulk transcriptomic perturbation resources reveals complementary therapeutic spaces for drug repurposing.bioRxiv : the preprint server for biology · 2026Article
- Spatial ecology of breast cancer reveals co-evolution of proliferative and dormant niches.Genome medicine · 2026Article
- RAG: a regularized adaptive graph-based method for rare-cell identification from single-cell expression data.Briefings in bioinformatics · 2026Article
- Dissecting autonomous enzymatic variability in single cells.Nature communications · 2026Article
- HNPP: Higher-order network-based personalized PageRank for detecting critical phase in complex biological systems.PLoS computational biology · 2026Article
- DISCERN: inferring drug sensitivity from single-cell transcriptomes using cell-type-specific genetic interaction networks.Genome medicine · 2026Article
- Rewiring tumor metabolism: heterogeneity, oncometabolites, and adaptive plasticity.Experimental hematology & oncology · 2026Review
- Therapy-Driven Molecular Evolution of Bladder Cancer: Roles of Cellular Plasticity and Tumor Microenvironment.International journal of molecular sciences · 2026Review
- Challenges and progress in RNA velocity: Comparative analysis across multiple biological contexts.PLoS computational biology · 2026Article
- FourierDrug: a domain generalization framework for robust drug response prediction via frequency-space asymmetric attention.Bioinformatics (Oxford, England) · 2026Article
- scRADAR: Dissecting intratumoral drug response heterogeneity at single-cell resolution via mechanism-guided prototype routing.PLoS computational biology · 2026Article
- Single-cell transcriptomics reveals a differential response of human bronchial epithelial cell-types to cadmium chloride.Archives of toxicology · 2026Article
- Single-Cell Computational Frameworks for Quantifying BET Bromodomain Inhibitor Resistance and Screening Re-Sensitizer Drugs in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrative Transcriptomic Analysis Identifies COL3A1 as a Potential Tumor-Intrinsic Therapeutic Target in NSCLC.Biomedicines · 2026Article
- CellMate─A Deep Learning-Assisted Single-Cell Data Processing Platform.Analytical chemistry · 2026Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors. These subpopulations exhibit epigenetic changes and differential therapeutic sensitivity. Recurrently overrepresented ontologies in genes that are differentially expressed between drug tolerant cell populations and drug sensitive cells include epithelial-to-mesenchymal transition, epithelium development, vesicle mediated transport, drug metabolism and cholesterol homeostasis. We show analysis of identified markers using the LINCS database to predict and functionally validate small molecules that target selected drug tolerant cell populations. In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones. In this study, we describe the spectrum of changes associated with drug tolerance and inhibition of specific tolerant cell subpopulations with combination agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.