Evidence map›Paper›PMID 38848360›Full record

ArticleScience advances2024

Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.

James H Park, Parvinder Hothi, Adrian Lopez Garcia de Lomana, Min Pan, Rachel Calder, Serdar Turkarslan, Wei-Ju Wu, Hwahyung Lee, Anoop P Patel, Charles Cobbs and 2 more

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. FeBioactive materials · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

James H ParkInstitute for Systems Biology, Seattle, WA, USA.ORCID 0000-0002-0006-7278
Parvinder HothiIvy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA, USA.ORCID 0009-0003-0977-0562
Adrian Lopez Garcia de LomanaCenter for Systems Biology, University of Iceland, Reykjavik, Iceland.ORCID 0000-0002-9748-347X
Min PanInstitute for Systems Biology, Seattle, WA, USA.ORCID 0000-0002-9781-0637
Rachel CalderInstitute for Systems Biology, Seattle, WA, USA.ORCID 0009-0008-1115-1046
Serdar TurkarslanInstitute for Systems Biology, Seattle, WA, USA.ORCID 0000-0003-1679-6405
Wei-Ju WuInstitute for Systems Biology, Seattle, WA, USA.ORCID 0000-0002-0022-2602
Hwahyung LeeIvy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA, USA.ORCID 0009-0003-2212-9462
Anoop P PatelDepartment of Neurosurgery, Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.
Charles CobbsIvy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA, USA.ORCID 0000-0001-7688-4293
Sui HuangInstitute for Systems Biology, Seattle, WA, USA.ORCID 0000-0002-3545-4665
Nitin S BaligaInstitute for Systems Biology, Seattle, WA, USA.ORCID 0000-0001-9157-5974

Funding

A systems analysis of drug tolerance in Mycobacterium tuberculosisR01AI128215 · NIAID · INSTITUTE FOR SYSTEMS BIOLOGY · PI Nitin S Baliga · 2017 to 2026
$8.8M
Site Specific Immunophenotyping Assays of COVID19 Patients to Align with NIAID National StudyR01AI141953 · NIAID · INSTITUTE FOR SYSTEMS BIOLOGY · PI BALIGA, NITIN S · 2019 to 2023
$5.7M
Systems biology of intratumoral heterogeneity in glioblastomaR01CA259469 · NCI · INSTITUTE FOR SYSTEMS BIOLOGY · PI Nitin S Baliga, CHARLES S COBBS · 2022 to 2026
$3.7M
Defining cellular states of quiescence in human brain tumorsR01NS119650 · NINDS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PADDISON, PATRICK · 2021 to 2025
$2.6M
Instability of Cancer Cell States in Tumor progression (ICCS)R01CA255536 · NCI · INSTITUTE FOR SYSTEMS BIOLOGY · PI BROCK, AMY, HUANG, SUI · 2021 to 2025
$2.5M
The Allee Effect in Tumor InitiationR01CA226258 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI BROCK, AMY, HUANG, SUI · 2018 to 2022
$2.3M
Dynamics of Non-equalibrium Cell State Transitions in Cell PopulationsR01GM109964 · NIGMS · INSTITUTE FOR SYSTEMS BIOLOGY · PI HUANG, SUI · 2015 to 2019
$1.7M
Theory and Measurement of Cell Population Dynamics with Cell-Cell Interaction (TMCC)R01GM135396 · NIGMS · INSTITUTE FOR SYSTEMS BIOLOGY · PI HUANG, SUI · 2019 to 2022
$1.7M
A systems approach to understanding overall drug response in a heterogeneous tumor-cell populationF32CA247445 · NCI · INSTITUTE FOR SYSTEMS BIOLOGY · PI PARK, JAMES HYUN-WOO · 2020 to 2022
$212k
NCI NIH HHS F32 CA247445NCI NIH HHS R01 CA226258NCI NIH HHS R01 CA255536NCI NIH HHS R01 CA259469NIAID NIH HHS R01 AI128215NIAID NIH HHS R01 AI141953NIGMS NIH HHS R01 GM109964NIGMS NIH HHS R01 GM135396NINDS NIH HHS R01 NS119650
6 · The paper itself

Abstract

Poor prognosis and drug resistance in glioblastoma (GBM) can result from cellular heterogeneity and treatment-induced shifts in phenotypic states of tumor cells, including dedifferentiation into glioma stem-like cells (GSCs). This rare tumorigenic cell subpopulation resists temozolomide, undergoes proneural-to-mesenchymal transition (PMT) to evade therapy, and drives recurrence. Through inference of transcriptional regulatory networks (TRNs) of patient-derived GSCs (PD-GSCs) at single-cell resolution, we demonstrate how the topology of transcription factor interaction networks drives distinct trajectories of cell-state transitions in PD-GSCs resistant or susceptible to cytotoxic drug treatment. By experimentally testing predictions based on TRN simulations, we show that drug treatment drives surviving PD-GSCs along a trajectory of intermediate states, exposing vulnerability to potentiated killing by siRNA or a second drug targeting treatment-induced transcriptional programs governing nongenetic cell plasticity. Our findings demonstrate an approach to uncover TRN topology and use it to rationally predict combinatorial treatments that disrupt acquired resistance in GBM.

Indexed as

Drug Resistance, NeoplasmGene Expression Regulation, NeoplasticGene Regulatory NetworksGliomaNeoplastic Stem CellsBrain NeoplasmsCell Line, TumorGlioblastomaHumansTemozolomideTemozolomide

Identifiers

PMID38848360
PMCPMC11160475

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Registered trials

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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.