Evidence map›Paper›PMID 27044097›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages.

Teresa E Peterson, Nathaniel D Kirkpatrick, Yuhui Huang, Christian T Farrar, Koen A Marijt, Jonas Kloepper, Meenal Datta, Zohreh Amoozgar, Giorgio Seano, Keehoon Jung and 13 more

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
198citing papers in PubMed, 2 pooled it
18.7field-weighted citation impact, top 1% 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

198 citing papers in PubMed, 2 syntheses or guidelines pooled it, 304 citations in OpenAlex.

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  6. Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019
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  14. The Role of CRISPR and Its Therapeutic Applications in Glioblastoma.International journal of molecular sciences · 2026
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138 more citing papers are in PubMed but not listed here.

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

23 authors at 3 institutions in 1 country.

Teresa E PetersonEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; Department of Biological Chemistry and Molecular Pharmacology, Harvard University, Boston, MA 02115;
Nathaniel D KirkpatrickEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Yuhui HuangEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Christian T FarrarAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129;
Koen A MarijtEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Jonas KloepperEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Meenal DattaEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; Department of Chemical and Biological Engineering, Tufts University, Medford, MA 02155;
Zohreh AmoozgarEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Giorgio SeanoEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Keehoon JungEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Walid S KamounEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Trupti VardamEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Matija SnuderlEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Jermaine GoveiaEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Sampurna ChatterjeeEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Ana BatistaEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Alona MuzikanskyBiostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston; MA 02114;
Ching Ching LeowDepartment of Translational Medicine Oncology, MedImmune, Gaithersburg, MD 20878;
Lei XuEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Tracy T BatchelorStephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.
Dan G DudaEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;
Dai FukumuraEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; dai@steele.mgh.harvard.edu jain@steele.mgh.harvard.edu.
Rakesh K JainEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; dai@steele.mgh.harvard.edu jain@steele.mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · USAthinoula A. Martinos Center for Biomedical Imaging · US

Funding

Vascular Normalization: Rolse of Perivascular CellsP01CA080124 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI · 2000 to 2016
$35.0M
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Benjamin Harris Kann · 2013 to 2026
$33.5M
Probing Tumor Microenvironment Using NanotechnologyR01CA126642 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2008 to 2012
$8.3M
Dissecting Pediatric Brain Tumor Microenvironment to Improve TreatmentR35CA197743 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2015 to 2020
$5.7M
NO in Tumor Angiogenesis,Microcirculation &Rad.TherapyR01CA096915 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI · 2002 to 2012
$3.0M
Clinical and Molecular Studies of Novel Therapeutics in Malignant Brain TumorsK24CA125440 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BATCHELOR, TRACY T · 2007 to 2016
$1.9M
Role of SDF1a pathway in prostate cancer relapse and metastasis post-radiotherapyR01CA159258 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DUDA, DAN GABRIEL · 2011 to 2015
$1.6M
Doppler Optical Frequency Domain Imaging InstrumentS10RR027070 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI · 2010 to 2010
$260k
NCI NIH HHS K24 CA125440NCI NIH HHS P01 CA080124NCI NIH HHS P01-CA080124NCI NIH HHS P50 CA165962NCI NIH HHS P50CA165962NCI NIH HHS R01 CA096915NCI NIH HHS R01-CA096915NCI NIH HHS R01 CA126642NCI NIH HHS R01CA126642NCI NIH HHS R01 CA159258NCI NIH HHS R01-CA159258NCI NIH HHS R35 CA197743NCI NIH HHS R35CA197743NCRR NIH HHS S10 RR027070NCRR NIH HHS S10-RR027070
6 · The paper itself

Abstract

Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2) compromises the benefits of anti-VEGF receptor (VEGFR) treatment in murine GBM models and that circulating Ang-2 levels in GBM patients rebound after an initial decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor) administration. Here we tested whether dual inhibition of VEGFR/Ang-2 could improve survival in two orthotopic models of GBM, Gl261 and U87. Dual therapy using cediranib and MEDI3617 (an anti-Ang-2-neutralizing antibody) improved survival over each therapy alone by delaying Gl261 growth and increasing U87 necrosis, effectively reducing viable tumor burden. Consistent with their vascular-modulating function, the dual therapies enhanced morphological normalization of vessels. Dual therapy also led to changes in tumor-associated macrophages (TAMs). Inhibition of TAM recruitment using an anti-colony-stimulating factor-1 antibody compromised the survival benefit of dual therapy. Thus, dual inhibition of VEGFR/Ang-2 prolongs survival in preclinical GBM models by reducing tumor burden, improving normalization, and altering TAMs. This approach may represent a potential therapeutic strategy to overcome the limitations of anti-VEGFR monotherapy in GBM patients by integrating the complementary effects of anti-Ang2 treatment on vessels and immune cells.

Indexed as

GlioblastomaMacrophagesNeoplasm ProteinsNeoplasms, ExperimentalNeovascularization, PathologicReceptors, Vascular Endothelial Growth FactorRibonuclease, PancreaticAnimalsAntibodies, NeoplasmCell Line, TumorDrug Screening Assays, AntitumorIndolesMiceQuinazolinesAng2 protein, mouseAntibodies, NeoplasmcediranibIndolesNeoplasm ProteinsQuinazolinesReceptors, Vascular Endothelial Growth FactorRibonuclease, Pancreaticanti-angiogenic therapycolony-stimulating factor 1macrophagetumor immunitytumor microenvironment

Identifiers

PMID27044097
PMCPMC4843449
OpenAlexW2328171087

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.