ArticleProceedings of the National Academy of Sciences of the United States of America2013
Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,071 papers, 2 of them syntheses that pooled it.
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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.
The trial behind it
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
1,071 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,734 citations in OpenAlex.
- Efficacy and safety of tyrosine kinase inhibitor combination therapy for glioblastoma: a meta-analysis with trial sequential analysis of randomized controlled trials.Frontiers in oncology · 2026Pooled it
- The Three Pillars of Glioblastoma: A Systematic Review and Novel Analysis of Multi-Omics and Clinical Data.Cells · 2024Pooled it
- A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification.Cancer medicine · 2023Trial
- Structural optimization of CHI3L1 inhibitors with improved pharmacokinetics and functional activity in 3D glioblastoma models.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Article
- Effects of borneol on pharmacokinetics and tissue distribution of tetramethylpyrazine in transdermal patch.Drug delivery and translational research · 2026Article
- Proteomic profiling of CD133 + and CD326 + (EpCAM) subpopulations in A549 cells: insights into pluripotency and tumor heterogeneity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Integrating Radiogenomics and CSF-Based Liquid Biopsy Sequencing for Precision Neuro-Oncology.International journal of molecular sciences · 2026Review
- Focused Ultrasound-Induced Mechanical Ablation Affects the Carbohydrate Metabolism of Residual/Peri-Focally Localized Glioblastoma Cells.International journal of cancer · 2026Article
- Targeting mitotic kinesin KIF20A: A differentiation-based therapeutic strategy for glioblastoma stem/progenitor cells.Stem cell reports · 2026Article
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Beyond the Brain: Circulating Tumor Cells as a Tool for Diagnosis and Monitoring.JCO precision oncology · 2026Article
- Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- Spatial and single-cell characterization of human glioblastoma tumor microenvironment reveals malignant cellular communities.Nature neuroscience · 2026Article
- Reassessing Viral Gene Therapy for Glioblastoma: Translational Opportunities and Challenges.The Yale journal of biology and medicine · 2026Article
- Brain Cancer: Molecular Alterations and Emerging Trends in Neuropharmacology.International journal of molecular sciences · 2026Review
- Peptides from the Shadows: Molecular Depth Insights and Clinical Horizons of Circular RNA-encoded Peptides in Gliomas.Neuromolecular medicine · 2026Review
- An oncostatin M receptor and chloride intracellular channel 1 crosstalk drives key oncogenic pathways in glioblastoma.Signal transduction and targeted therapy · 2026Article
- Molecular features unique to circulating tumor DNA enable the tumor-naïve liquid biopsy of glioblastoma.NPJ precision oncology · 2026Article
- The promising role of cathepsins as biomarkers and therapeutic targets in glioblastoma.Discover oncology · 2026Review
1,011 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure. However, the extent of intratumor heterogeneity as a result of tumor evolution is still poorly understood. To address this, we developed a unique surgical multisampling scheme to collect spatially distinct tumor fragments from 11 GB patients. We present an integrated genomic analysis that uncovers extensive intratumor heterogeneity, with most patients displaying different GB subtypes within the same tumor. Moreover, we reconstructed the phylogeny of the fragments for each patient, identifying copy number alterations in EGFR and CDKN2A/B/p14ARF as early events, and aberrations in PDGFRA and PTEN as later events during cancer progression. We also characterized the clonal organization of each tumor fragment at the single-molecule level, detecting multiple coexisting cell lineages. Our results reveal the genome-wide architecture of intratumor variability in GB across multiple spatial scales and patient-specific patterns of cancer evolution, with consequences for treatment design.
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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.