Evidence map›Paper›PMID 25522764›Full record

ArticleMolecular cancer therapeutics2015

Radiotherapy followed by aurora kinase inhibition targets tumor-propagating cells in human glioblastoma.

Nan Li, Dustin J Maly, Yvan H Chanthery, Daniel W Sirkis, Jean L Nakamura, Mitchel S Berger, C David James, Kevan M Shokat, William A Weiss, Anders I Persson

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

Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

18 citing papers in PubMed, 26 citations in OpenAlex.

  1. Chromosomal Instability Drives Glioblastoma Heterogeneity and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

10 authors at 1 institution in 1 country.

Nan LiDepartment of Neurology, University of California, San Francisco, California. Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, California. Sandler Neurosciences Center, University of California, San Francisco, California.
Dustin J MalyDepartment of Chemistry, University of Washington, Seattle, Washington.
Yvan H ChantheryDepartment of Neurology, University of California, San Francisco, California. Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, California. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Daniel W SirkisDepartment of Neurology, University of California, San Francisco, California. Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, California. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Jean L NakamuraHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. Department of Radiation Oncology, University of California, San Francisco, California.
Mitchel S BergerDepartment of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, California. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
C David JamesDepartment of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, California. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Kevan M ShokatChemistry and Chemical Biology Graduate Program, Howard Hughes Medical Institute, University of California, San Francisco, California.
William A WeissDepartment of Neurology, University of California, San Francisco, California. Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, California. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Anders I PerssonDepartment of Neurology, University of California, San Francisco, California. Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, California. Sandler Neurosciences Center, University of California, San Francisco, California. Anders.Persson@ucsf.edu.
University of California, San Francisco · US

Funding

The vascular niche in glioma propagation and resistance to therapyU54CA163155 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEISS, WILLIAM A · 2011 to 2015
$4.4M
Genetic network analysis of cancer targetsU01CA176287 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEISS, WILLIAM A · 2013 to 2016
$1.2M
Antisecretory factor as a novel therapeutic agent in human glioblastomaR21NS088114 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PERSSON, PER ANDERS INGEMAR · 2014 to 2015
$395k
Howard Hughes Medical InstituteNCI NIH HHS U01 CA176287NCI NIH HHS U01CA176287NCI NIH HHS U54 CA163155NCI NIH HHS U54CA163155NINDS NIH HHS R21 NS088114NINDS NIH HHS R21NS088114
6 · The paper itself

Abstract

Glioblastoma (GBM) is the most common malignant primary brain tumor. Radiotherapy fails to eliminate subpopulations of stem-like tumor-propagating cells (TPC), resulting in tumor regrowth. To identify kinases that promote TPC self-renewal rather than increasing proliferation in human GBM cultures, we screened a library of 54 nonselective tool compounds and determined their kinase inhibitor profiles in vitro. Most compounds inhibited aurora kinase (AURK) activity and blocked TPC self-renewal, while inducing GBM cell polynucleation and apoptosis. To prevent regrowth by TPCs, we used a priming dose of radiation followed by incubation with the pan-AURK inhibitor VX680 to block self-renewal and induce apoptosis in GBM cultures. In mice xenografted with human GBM cells, radiotherapy followed by VX680 treatment resulted in reduced tumor growth and increased survival relative to either monotherapy alone or VX680 treatment before radiation. Our results indicate that AURK inhibition, subsequent to radiation, may enhance the efficacy of radiotherapy by targeting radioresistant TPCs in human GBMs.

Indexed as

AnimalsApoptosisAurora KinasesBiomarkers, TumorBrain NeoplasmsCell Cycle CheckpointsCell ProliferationDrug Screening Assays, AntitumorGlioblastomaHistonesHumansMembrane GlycoproteinsMice, NudeNeoplastic Stem CellsPhosphorylationPodoplaninAurora KinasesBiomarkers, TumorHistonesMembrane GlycoproteinsPDPN protein, humanPodoplaninProtein Kinase Inhibitors

Identifiers

PMID25522764
PMCPMC4326592
OpenAlexW2161371354

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.