Evidence map›Paper›PMID 27825958›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2016

Simultaneous blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme.

Szu-Ting Chou, Rameshwar Patil, Anna Galstyan, Pallavi R Gangalum, Webster K Cavenee, Frank B Furnari, Vladimir A Ljubimov, Alexandra Chesnokova, Andrei A Kramerov, Hui Ding and 7 more

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

Article in Journal of controlled release : official journal of the Controlled Release Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

35 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Antibody-conjugated polymer nanoparticles for brain cancer.Drug delivery and translational research · 2025
    Review
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  5. Regulation of cancer progression by CK2: an emerging therapeutic target.Medical oncology (Northwood, London, England) · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Szu-Ting Chou *Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Rameshwar Patil *Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Anna Galstyan *Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Pallavi R GangalumNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Webster K CaveneeLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, California, USA.
Frank B FurnariLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, California, USA.
Vladimir A LjubimovNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Alexandra ChesnokovaNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Andrei A KramerovRegenerative Medicine Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Hui DingNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Vida FalahatianDuke University School of Medicine, Department of Biostatistic and Bioinformatics Clinical Research Training Program ( CRTP ).
Leila MashoufJohns Hopkins University, Baltimore, Maryland, USA.
Irving FoxNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Keith L BlackNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Eggehard HollerNanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Alexander V Ljubimov *Regenerative Medicine Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Julia Y Ljubimova *Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Cedars-Sinai Medical Center · USUniversity of California San Diego · USDuke University · USJohns Hopkins University · US

Funding

Mechanisms of Epithelial Alterations in Diabetic CorneaR01EY013431 · NEI · CEDARS-SINAI MEDICAL CENTER · PI Alexander V Ljubimov · 2001 to 2026
$11.3M
Novel Nanopolymers to Inhibit Angiogenesis and Increase the Anti-tumor ImmunityR01CA136841 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LJUBIMOVA, JULIA Y, PENICHET, MANUEL L · 2010 to 2014
$2.7M
Nanoconjugate based on polymalic acid for brain tumor treatmentU01CA151815 · NCI · CEDARS-SINAI MEDICAL CENTER · PI LJUBIMOVA, JULIA Y · 2010 to 2014
$2.7M
Glial tumor image-guided surgery and treatmentR01CA209921 · NCI · TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION · PI HOLLER, EGGEHARD · 2016 to 2021
$2.6M
Differential MRI imaging for brain tumor metastases diagnosis and treatment monitoringR01CA188743 · NCI · CEDARS-SINAI MEDICAL CENTER · PI LJUBIMOVA, JULIA Y · 2015 to 2019
$2.5M
NCI NIH HHS R01 CA136841NCI NIH HHS R01 CA188743NCI NIH HHS R01 CA209921NCI NIH HHS U01 CA151815NEI NIH HHS R01 EY013431
6 · The paper itself

Abstract

Glioblastoma multiforme (GBM) remains the deadliest brain tumor in adults. GBM tumors are also notorious for drug and radiation resistance. To inhibit GBMs more effectively, polymalic acid-based blood-brain barrier crossing nanobioconjugates were synthesized that are delivered to the cytoplasm of cancer cells and specifically inhibit the master regulator serine/threonine protein kinase CK2 and the wild-type/mutated epidermal growth factor receptor (EGFR/EGFRvIII), which are overexpressed in gliomas according to The Cancer Genome Atlas (TCGA) GBM database. Two xenogeneic mouse models bearing intracranial human GBMs from cell lines LN229 and U87MG that expressed both CK2 and EGFR at different levels were used. Simultaneous knockdown of CK2α and EGFR/EGFRvIII suppressed their downstream prosurvival signaling. Treatment also markedly reduced the expression of programmed death-ligand 1 (PD-L1), a negative regulator of cytotoxic lymphocytes. Downregulation of CK2 and EGFR also caused deactivation of heat shock protein 90 (Hsp90) co-chaperone Cdc37, which may suppress the activity of key cellular kinases. Inhibition of either target was associated with downregulation of the other target as well, which may underlie the increased efficacy of the dual nanobioconjugate that is directed against both CK2 and EGFR. Importantly, the single nanodrugs, and especially the dual nanodrug, markedly suppressed the expression of the cancer stem cell markers c-Myc, CD133, and nestin, which could contribute to the efficacy of the treatments. In both tumor models, the nanobioconjugates significantly increased (up to 2-fold) animal survival compared with the PBS-treated control group. The versatile nanobioconjugates developed in this study, with the abilities of anti-cancer drug delivery across biobarriers and the inhibition of key tumor regulators, offer a promising nanotherapeutic approach to treat GBMs, and to potentially prevent drug resistance and retard the recurrence of brain tumors.

Indexed as

AdultAnimalsAntibodies, MonoclonalAntineoplastic AgentsBlood-Brain BarrierBrain NeoplasmsCasein Kinase IICell Line, TumorErbB ReceptorsFemaleGlioblastomaHumansMalatesMiceMice, NudeNanoconjugatesAntibodies, MonoclonalAntineoplastic AgentsCasein Kinase IIepidermal growth factor receptor VIIIErbB ReceptorsMalatesNanoconjugatesOligonucleotides, AntisensePolyethylene Glycolspoly(malic acid)PolymersBlood-brain barrier deliveryDual antisense oligonucleotide-dual antibody nanobioconjugateEGFR/EGFRvIIIGlioblastoma multiformeProtein kinase CK2

Identifiers

PMID27825958
PMCPMC5308909
OpenAlexW2548516618

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.