Evidence map›Paper›PMID 28057017›Full record

ArticleJournal of hematology & oncology2017

The brain-penetrating CXCR4 antagonist, PRX177561, increases the antitumor effects of bevacizumab and sunitinib in preclinical models of human glioblastoma.

Giovanni Luca Gravina, Andrea Mancini, Francesco Marampon, Alessandro Colapietro, Simona Delle Monache, Roberta Sferra, Flora Vitale, Peter J Richardson, Lee Patient, Stephen Burbidge and 1 more

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

Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

49 citing papers in PubMed, 70 citations in OpenAlex.

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  12. CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.Journal of cancer research and clinical oncology · 2023
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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

11 authors at 1 institution in 1 country.

Giovanni Luca GravinaDepartment of Biotechnological and Applied Clinical Sciences, Neurobiology Laboratory, University of L'Aquila, Via vetoios snc, Coppito II, L'Aquila, Italy.
Andrea ManciniDepartment of Biotechnological and Applied Clinical Sciences, Neurobiology Laboratory, University of L'Aquila, Via vetoios snc, Coppito II, L'Aquila, Italy.
Francesco MaramponDepartment of Biotechnological and Applied Clinical Sciences, Neurobiology Laboratory, University of L'Aquila, Via vetoios snc, Coppito II, L'Aquila, Italy.
Alessandro ColapietroDepartment of Biotechnological and Applied Clinical Sciences, Neurobiology Laboratory, University of L'Aquila, Via vetoios snc, Coppito II, L'Aquila, Italy.
Simona Delle MonacheDepartment of Biotechnological and Applied Clinical Sciences, Neurobiology Laboratory, University of L'Aquila, Via vetoios snc, Coppito II, L'Aquila, Italy.
Roberta SferraDepartment of Biotechnological and Applied Clinical Sciences, Neurobiology Laboratory, University of L'Aquila, Via vetoios snc, Coppito II, L'Aquila, Italy.
Flora VitaleDepartment of Biotechnological and Applied Clinical Sciences, Neurobiology Laboratory, University of L'Aquila, Via vetoios snc, Coppito II, L'Aquila, Italy.
Peter J RichardsonProximagen Ltd., Babraham Research Campus, Cambridge, CB22 3AT, UK.
Lee PatientProximagen Ltd., Babraham Research Campus, Cambridge, CB22 3AT, UK.
Stephen BurbidgeProximagen Ltd., Babraham Research Campus, Cambridge, CB22 3AT, UK.
Claudio FestucciaDepartment of Biotechnological and Applied Clinical Sciences, Neurobiology Laboratory, University of L'Aquila, Via vetoios snc, Coppito II, L'Aquila, Italy. Claudio.festuccia@univaq.it.
University of L'Aquila · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlioblastoma recurrence after treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision and chemotherapy ineffective. It has been demonstrated that anti-VEGF/VEGFR therapies control the invasive phenotype and that relapse occurs through the increased activity of CXCR4. We therefore hypothesized that combining bevacizumab or sunitinib with the novel CXCR4 antagonist, PRX177561, would have superior antitumor activity.

methodsThe effects of bevacizumab, sunitinib, and PRX177561 were tested alone or in combination in subcutaneous xenografts of U87MG, U251, and T98G cells as well as on intracranial xenografts of luciferase tagged U87MG cells injected in CD1-nu/nu mice. Animals were randomized to receive vehicle, bevacizumab (4 mg/kg iv every 4 days), sunitinib (40 mg/kg po qd), or PRX177561 (50 mg/kg po qd).

resultsThe in vivo experiments demonstrated that bevacizumab and sunitinib increase the in vivo expression of CXCR4, SDF-1α, and TGFβ1. In addition, we demonstrate that the co-administration of the novel brain-penetrating CXCR4 antagonist, PRX177561, with bevacizumab or sunitinib inhibited tumor growth and reduced the inflammation. The combination of PRX177561 with bevacizumab resulted in a synergistic reduction of tumor growth with an increase of disease-free survival (DSF) and overall survival (OS), whereas the combination of PRX177561 with sunitinib showed a mild additive effect.

conclusionsThe CXC4 antagonist PRX177561 may be a valid therapeutic complement to anti-angiogenic therapy, particularly when used in combination with VEGF/VEGFR inhibitors. Therefore, this compound deserves to be considered for future clinical evaluation.

Indexed as

Angiogenesis InhibitorsAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBrainBrain NeoplasmsCell Line, TumorDrug Evaluation, PreclinicalDrug InteractionsDrug SynergismGlioblastomaHeterograftsHumansIndolesMiceAngiogenesis InhibitorsAntineoplastic AgentsBevacizumabCXCR4 protein, humanIndolesPyrrolesReceptors, CXCR4SunitinibBevacizumabCXCR4GlioblastomaSunitinib

Identifiers

PMID28057017
PMCPMC5217647
OpenAlexW2568132954

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.