ArticleCancers2019
Intratumoural Heterogeneity Underlies Distinct Therapy Responses and Treatment Resistance in Glioblastoma.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- GFAP-Dependent Transcriptional Dynamics and Cellular Heterogeneity in Primary, Recurrent, and Grade III Gliomas.Cancer informatics · 2026Article
- Spatial pharmacology of anti-cancer immunomodulators: a comprehensive review.Frontiers in pharmacology · 2026Review
- Nanocarrier Strategies in Glioblastoma: Overcoming Barriers to Effective Brain Tumor Therapy.AAPS PharmSciTech · 2025Review
- Whole genome sequencing-based analysis of genetic predisposition to adult glioblastoma.NPJ genomic medicine · 2025Article
- A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomide.Scientific reports · 2025Article
- Understanding cellular proliferation activity in breast cancer using multi-compartment model of transverse relaxation time mapping on 3T MRI.Frontiers in oncology · 2025Article
- DNA methylation heterogeneity attributable to a complex tumor immune microenvironment prompts prognostic risk in glioma.Epigenetics · 2024Article
- Identification and Verification of Key Genes Associated with Temozolomide Resistance in Glioblastoma Based on Comprehensive Bioinformatics Analysis.Iranian journal of biotechnology · 2024Article
- Review
- Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients.Genes · 2023Article
- Review
- Generalising uncertainty improves accuracy and safety of deep learning analytics applied to oncology.Scientific reports · 2023Article
- The Sesquiterpene Lactone Cynaropicrin Manifests Strong Cytotoxicity in Glioblastoma Cells U-87 MG by Induction of Oxidative Stress.Biomedicines · 2022Article
- MGMT and Whole-Genome DNA Methylation Impacts on Diagnosis, Prognosis and Therapy of Glioblastoma Multiforme.International journal of molecular sciences · 2022Review
- If Artificial In Vitro Microenvironment Can Influence Tumor Drug Resistance Network via Modulation of lncRNA Expression?-Comparative Analysis of Glioblastoma-Derived Cell Culture Models and Initial Tumors In Vivo.Cellular and molecular neurobiology · 2022Article
- Engineering Novel Lentiviral Vectors for Labelling Tumour Cells and Oncogenic Proteins.Bioengineering (Basel, Switzerland) · 2022Article
- Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors.Cancers · 2022Review
- AZD3759 inhibits glioma through the blockade of the epidermal growth factor receptor and Janus kinase pathways.Bioengineered · 2021Article
- Review
- Review
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 4 institutions in 1 country.
Funding
Abstract
Glioblastomas are the most common and lethal neoplasms of the central nervous system. Neighbouring glioma cells maintain extreme degrees of genetic and phenotypic variation that form intratumoural heterogeneity. This genetic diversity allows the most adaptive tumour clones to develop treatment resistance, ultimately leading to disease recurrence. We aimed to model this phenomenon and test the effectiveness of several targeted therapeutic interventions to overcome therapy resistance. Heterogeneous tumour masses were first deconstructed into single tumour cells, which were expanded independently as single-cell clones. Single nucleotide polymorphism arrays, whole-genome and RNA sequencing, and CpG methylation analysis validated the unique molecular profile of each tumour clone, which displayed distinct pathologic features, including cell morphology, growth rate, and resistance to temozolomide and ionizing radiation. We also identified variable sensitivities to AURK, CDK, and EGFR inhibitors which were consistent with the heterogeneous molecular alterations that each clone harboured. These targeted therapies effectively eliminated the temozolomide- and/or irradiation-resistant clones and also parental polyclonal cells. Our findings indicate that polyclonal tumours create a dynamic environment that consists of diverse tumour elements and treatment responses. Designing targeted therapies based on a range of molecular profiles can be a more effective strategy to eradicate treatment resistance, recurrence, and metastasis.
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What OpenQuestion holds
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.