Trial reportGenome medicine2020
Single-cell RNA sequencing reveals the tumor microenvironment and facilitates strategic choices to circumvent treatment failure in a chemorefractory bladder cancer patient.
Trial report in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 194 citations in OpenAlex.
- Single-cell RNA sequencing reveals the tumor microenvironment and facilitates strategic choices to circumvent treatment failure in a chemorefractory bladder cancer patient.Genome medicine · 2020Trial
- Comprehensive overview of AI methodologies in nano-drug delivery Optimization and Design.NPJ precision oncology · 2026Review
- An Intravesical Akkermansia muciniphila-Based Chemo-Immunotherapeutic Platform for Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Single-cell transcriptome analysis in ovarian steroid cell tumors-not otherwise specified.Journal of ovarian research · 2026Article
- Joint Low Rank Representation with Symmetric Orthogonal Decomposition for Clustering of scRNA-seq Data.Interdisciplinary sciences, computational life sciences · 2026Article
- Basal cell subsets, as biomarker to predict the therapeutic effect of neoadjuvant therapy for esophageal carcinoma.Journal of cancer research and clinical oncology · 2026Article
- Single-cell insights into cisplatin resistance mechanisms in bladder cancer tumor microenvironment.The Journal of biological chemistry · 2026Article
- Multi-organ single-cell analysis of preferential expression of CAKUT genes.BMC nephrology · 2026Article
- Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- An integrative omics-guided druggability analysis of VCX2 in hepatocellular carcinoma using Peruvian natural products.Frontiers in bioinformatics · 2026Article
- Multi-Omics Analysis Reveals m7G Methylation-Related Genes May Be Involved in TGF-β Signaling-Mediated Anti-PD-L1 Response in Bladder Cancer.ImmunoTargets and therapy · 2026Article
- Article
- Targeting the SMAD3/CISD2 axis suppresses bladder cancer progression by promoting ferroptosis in mesenchymal-like bladder cancer cells.Cell death & disease · 2025Article
- Single-cell sequencing in bladder cancer: new insights from tumor cell diversity to individualized treatment strategies.Cancer cell international · 2025Review
- Pan-cancer gene set discovery via scRNA-seq for optimal deep learning based downstream tasks.Scientific reports · 2025Article
- Formononetin suppresses osteosarcoma by targeting MYO1B and remodeling the tumor immune microenvironment.APL bioengineering · 2025Article
- Comprehensive single-cell RNA analysis reveals intertumoral microenvironment heterogeneity and hub niche of carcinogenesis in thyroid cancer.NPJ precision oncology · 2025Article
- TGF-β signaling and tumor microenvironment dynamics in bladder cancer progression post-BCG therapy: a longitudinal single-nucleus RNA-seq study.BMC cancer · 2025Article
- Fragile X mental retardation 1 gene FMR1 promotes proliferation, migration, and invasion of gastric cancer cells via c-MYC.Journal of translational medicine · 2025Article
55 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
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor cell-intrinsic mechanisms and complex interactions with the tumor microenvironment contribute to therapeutic failure via tumor evolution. It may be possible to overcome treatment resistance by developing a personalized approach against relapsing cancers based on a comprehensive analysis of cell type-specific transcriptomic changes over the clinical course of the disease using single-cell RNA sequencing (scRNA-seq).
methodsHere, we used scRNA-seq to depict the tumor landscape of a single case of chemo-resistant metastatic, muscle-invasive urothelial bladder cancer (MIUBC) addicted to an activating Harvey rat sarcoma viral oncogene homolog (HRAS) mutation. In order to analyze tumor evolution and microenvironmental changes upon treatment, we also applied scRNA-seq to the corresponding patient-derived xenograft (PDX) before and after treatment with tipifarnib, a HRAS-targeting agent under clinical evaluation.
resultsIn the parallel analysis of the human MIUBC and the PDX, diverse stromal and immune cell populations recapitulated the cellular composition in the human and mouse tumor microenvironment. Treatment with tipifarnib showed dramatic anticancer effects but was unable to achieve a complete response. Importantly, the comparative scRNA-seq analysis between pre- and post-tipifarnib-treated PDX revealed the nature of tipifarnib-refractory tumor cells and the tumor-supporting microenvironment. Based on the upregulation of programmed death-ligand 1 (PD-L1) in surviving tumor cells, and the accumulation of multiple immune-suppressive subsets from post-tipifarnib-treated PDX, a PD-L1 inhibitor, atezolizumab, was clinically applied; this resulted in a favorable response from the patient with acquired resistance to tipifarnib.
conclusionWe presented a single case report demonstrating the power of scRNA-seq for visualizing the tumor microenvironment and identifying molecular and cellular therapeutic targets in a treatment-refractory cancer patient.
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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.