Evidence map›Paper›PMID 26965451›Full record

ArticleNeuro-oncology2016

Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models.

Yuji Piao, Soon Young Park, Verlene Henry, Bryan D Smith, Ningyi Tiao, Daniel L Flynn, John F de Groot

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

Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

43 citing papers in PubMed, 67 citations in OpenAlex.

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  17. Receptor Tyrosine Kinase Signaling and Targeting in Glioblastoma Multiforme.International journal of molecular sciences · 2021
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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

7 authors at 2 institutions in 1 country.

Yuji PiaoDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Y.P., S.Y.P., N.T., J.F.d.G.); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (V.H.); Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts (B.D.S., D.L.F.).
Soon Young ParkDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Y.P., S.Y.P., N.T., J.F.d.G.); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (V.H.); Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts (B.D.S., D.L.F.).
Verlene HenryDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Y.P., S.Y.P., N.T., J.F.d.G.); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (V.H.); Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts (B.D.S., D.L.F.).
Bryan D SmithDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Y.P., S.Y.P., N.T., J.F.d.G.); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (V.H.); Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts (B.D.S., D.L.F.).
Ningyi TiaoDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Y.P., S.Y.P., N.T., J.F.d.G.); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (V.H.); Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts (B.D.S., D.L.F.).
Daniel L FlynnDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Y.P., S.Y.P., N.T., J.F.d.G.); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (V.H.); Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts (B.D.S., D.L.F.).
John F de GrootDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (Y.P., S.Y.P., N.T., J.F.d.G.); Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (V.H.); Deciphera Pharmaceuticals, LLC, Waltham, Massachusetts (B.D.S., D.L.F.) jdegroot@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USDeciphera Pharmaceuticals (United States) · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Tropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo · 2008 to 2026
$41.2M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA127001
6 · The paper itself

Abstract

backgroundGlioblastoma highly expresses the proto-oncogene MET in the setting of resistance to bevacizumab. MET engagement by hepatocyte growth factor (HGF) results in receptor dimerization and autophosphorylation mediating tumor growth, invasion, and metastasis. Evasive revascularization and the recruitment of TIE2-expressing macrophages (TEMs) are also triggered by anti-VEGF therapy.

methodsWe investigated the activity of altiratinib (a novel balanced inhibitor of MET/TIE2/VEGFR2) against human glioblastoma stem cell lines in vitro and in vivo using xenograft mouse models. The biological activity of altiratinib was assessed in vitro by testing the expression of HGF-stimulated MET phosphorylation as well as cell viability after altiratinib treatment. Tumor volume, stem cell and mesenchymal marker levels, microvessel density, and TIE2-expressing monocyte infiltration were evaluated in vivo following treatment with a control, bevacizumab alone, bevacizumab combined with altiratinib, or altiratinib alone.

resultsIn vitro, HGF-stimulated MET phosphorylation was completely suppressed by altiratinib in GSC17 and GSC267, and altiratinib markedly inhibited cell viability in several glioblastoma stem cell lines. More importantly, in multiple xenograft mouse models, altiratinib combined with bevacizumab dramatically reduced tumor volume, invasiveness, mesenchymal marker expression, microvessel density, and TIE2-expressing monocyte infiltration compared with bevacizumab alone. Furthermore, in the GSC17 xenograft model, altiratinib combined with bevacizumab significantly prolonged survival compared with bevacizumab alone.

conclusionsTogether, these data suggest that altiratinib may suppress tumor growth, invasiveness, angiogenesis, and myeloid cell infiltration in glioblastoma. Thus, altiratinib administered alone or in combination with bevacizumab may overcome resistance to bevacizumab and prolong survival in patients with glioblastoma.

Indexed as

AnimalsAntineoplastic AgentsApoptosisBevacizumabBrain NeoplasmsCell ProliferationDrug Resistance, NeoplasmFemaleGlioblastomaHumansMiceMice, NudeNeoplasm InvasivenessNeovascularization, PathologicProtein Kinase InhibitorsProto-Oncogene MasAntineoplastic AgentsBevacizumabKDR protein, humanMAS1 protein, humanMET protein, humanProtein Kinase InhibitorsProto-Oncogene MasProto-Oncogene Proteins c-metReceptor, TIE-2Vascular Endothelial Growth Factor Receptor-2altiratinibbevacizumabgliomaMETTIE2–expressing monocytes

Identifiers

PMID26965451
PMCPMC4998992
OpenAlexW2338101963

What OpenQuestion holds

Textmetadata
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.