Evidence map›Paper›PMID 26059434›Full record

ArticleOncotarget2015

Orthogonal targeting of EGFRvIII expressing glioblastomas through simultaneous EGFR and PLK1 inhibition.

Ying Shen, Jie Li, Masayuki Nitta, Diahnn Futalan, Tyler Steed, Jeffrey M Treiber, Zack Taich, Deanna Stevens, Jill Wykosky, Hong-Zhuan Chen and 9 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 28% of its field
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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
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  7. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 3 countries.

Ying ShenCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA.
Jie LiCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA.
Masayuki NittaDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Diahnn FutalanCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA.
Tyler SteedCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA.
Jeffrey M TreiberCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA.
Zack TaichCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA.
Deanna StevensSan Diego Branch, Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, USA.
Jill WykoskySan Diego Branch, Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, USA.
Hong-Zhuan ChenDepartment of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bob S CarterCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA.
Oren J BecherDepartments of Pediatrics and Pathology, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA.
Richard KennedyCentre for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, UK.
Fumiko EsashiThe Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Jann N SarkariaDepartment of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
Frank B FurnariSan Diego Branch, Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, USA.
Webster K CaveneeSan Diego Branch, Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, USA.
Arshad DesaiSan Diego Branch, Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA, USA.
Clark C ChenCenter for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA.
University of California, San Diego · USLudwig Cancer Research · USShanghai Jiao Tong University · CNDana-Farber Cancer Institute · USDuke Medical Center · USMayo Clinic in Arizona · USQueen's University Belfast · GBUniversity of Oxford · GB

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Transgenic Mouse and Biobank CoreP01CA095616 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DEPINHO, RONALD ANTHONY · 2003 to 2012
$20.3M
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
Kinetochore Specification and FunctionR01GM074215 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DESAI, ARSHAD · 2005 to 2025
$8.2M
Genotypic Interactions in Brain Cancer HeterogeneityR01NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2012 to 2022
$3.5M
NCI NIH HHS P01 CA095616NCI NIH HHS P01-CA95616NIGMS NIH HHS R01 GM074215NIGMS NIH HHS T32 GM007198NIGMS NIH HHS T32 GM008666NINDS NIH HHS R01 NS080939NINDS NIH HHS R01-NS080939Wellcome Trust 101009
6 · The paper itself

Abstract

We identified a synthetic lethality between PLK1 silencing and the expression of an oncogenic Epidermal Growth Factor Receptor, EGFRvIII. PLK1 promoted homologous recombination (HR), mitigating EGFRvIII induced oncogenic stress resulting from DNA damage accumulation. Accordingly, PLK1 inhibition enhanced the cytotoxic effects of the DNA damaging agent, temozolomide (TMZ). This effect was significantly more pronounced in an Ink4a/Arf(-/-) EGFRvIII glioblastoma model relative to an Ink4a/Arf(-/-) PDGF-β model. The tumoricidal and TMZ-sensitizing effects of BI2536 were uniformly observed across Ink4a/Arf(-/-) EGFRvIII glioblastoma clones that acquired independent resistance mechanisms to EGFR inhibitors, suggesting these resistant clones retain oncogenic stress that required PLK1 compensation. Although BI2536 significantly augmented the anti-neoplastic effect of EGFR inhibitors in the Ink4a/Arf(-/-) EGFRvIII model, durable response was not achieved until TMZ was added. Our results suggest that optimal therapeutic effect against glioblastomas requires a "multi-orthogonal" combination tailored to the molecular physiology associated with the target cancer genome.

Indexed as

AnimalsAntineoplastic Agents, AlkylatingBlotting, WesternBrain NeoplasmsCell Cycle ProteinsCell Line, TumorComet AssayDacarbazineDNA DamageErbB ReceptorsFlow CytometryFluorescent Antibody TechniqueGene Knockout TechniquesGlioblastomaHeterograftsHumansAntineoplastic Agents, AlkylatingCell Cycle ProteinsDacarbazineepidermal growth factor receptor VIIIErbB ReceptorsPolo-Like Kinase 1Protein Serine-Threonine KinasesProto-Oncogene ProteinsRNA, Small InterferingTemozolomideEGFREGFRvIIIglioblastomasynthetic lethality

Identifiers

PMID26059434
PMCPMC4494902
OpenAlexW1576688694

What OpenQuestion holds

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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.