ArticlePLoS computational biology2012
In silico experimentation of glioma microenvironment development and anti-tumor therapy.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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.
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
14 citing papers in PubMed.
- Cancer-on-a-chip for precision cancer medicine.Lab on a chip · 2025Review
- Biosensor-Enhanced Organ-on-a-Chip Models for Investigating Glioblastoma Tumor Microenvironment Dynamics.Sensors (Basel, Switzerland) · 2024Review
- Tumor-associated microglia and macrophages in glioblastoma: From basic insights to therapeutic opportunities.Frontiers in immunology · 2022Review
- P4HA1 Down-Regulation Inhibits Glioma Invasiveness by Promoting M1 Microglia Polarization.OncoTargets and therapy · 2021Article
- A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma.Theranostics · 2021Review
- Revealing and Harnessing Tumour-Associated Microglia/Macrophage Heterogeneity in Glioblastoma.International journal of molecular sciences · 2020Review
- CD90 determined two subpopulations of glioma-associated mesenchymal stem cells with different roles in tumour progression.Cell death & disease · 2018Article
- Mathematical Modeling of Therapy-induced Cancer Drug Resistance: Connecting Cancer Mechanisms to Population Survival Rates.Scientific reports · 2016Article
- Cancer systems biology: embracing complexity to develop better anticancer therapeutic strategies.Oncogene · 2015Review
- A microchip platform for interrogating tumor-macrophage paracrine signaling at the single-cell level.Lab on a chip · 2014Article
- High-throughput secretomic analysis of single cells to assess functional cellular heterogeneity.Analytical chemistry · 2013Article
- Single-cell protein secretomic signatures as potential correlates to tumor cell lineage evolution and cell-cell interaction.Frontiers in oncology · 2013Article
- Microglia and macrophages in malignant gliomas: recent discoveries and implications for promising therapies.Clinical & developmental immunology · 2013Review
- Inter-cellular signaling network reveals a mechanistic transition in tumor microenvironment.Integrative biology : quantitative biosciences from nano to macro · 2012Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Tumor cells do not develop in isolation, but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors, forming a complex intercellular signaling network. Herein, we report an unbiased, generic model to integrate prior biochemical data and the constructed brain tumor microenvironment in silico as characterized by an intercellular signaling network comprising 5 types of cells, 15 cytokines, and 69 signaling pathways. The results show that glioma develops through three distinct phases: pre-tumor, rapid expansion, and saturation. We designed a microglia depletion therapy and observed significant benefit for virtual patients treated at the early stages but strikingly no therapeutic efficacy at all when therapy was given at a slightly later stage. Cytokine combination therapy exhibits more focused and enhanced therapeutic response even when microglia depletion therapy already fails. It was further revealed that the optimal combination depends on the molecular profile of individual patients, suggesting the need for patient stratification and personalized treatment. These results, obtained solely by observing the in silico dynamics of the glioma microenvironment with no fitting to experimental/clinical data, reflect many characteristics of human glioma development and imply new venues for treating tumors via selective targeting of microenvironmental components.
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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.