Evidence map›Paper›PMID 25534822›Full record

ArticleNeuro-oncology2015

Preclinical evaluation of dasatinib alone and in combination with cabozantinib for the treatment of diffuse intrinsic pontine glioma.

Nathalène Truffaux, Cathy Philippe, Janna Paulsson, Felipe Andreiuolo, Léa Guerrini-Rousseau, Gaétan Cornilleau, Ludivine Le Dret, Catherine Richon, Ludovic Lacroix, Stéphanie Puget and 4 more

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

Article in Neuro-oncology, 2015. 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
2.3field-weighted citation impact, top 12% 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, 67 citations in OpenAlex.

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  9. Advances in Treatment of Diffuse Midline Gliomas.Current neurology and neuroscience reports · 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

14 authors at 7 institutions in 2 countries.

Nathalène TruffauxCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Cathy PhilippeCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Janna PaulssonCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Felipe AndreiuoloCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Léa Guerrini-RousseauCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Gaétan CornilleauCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Ludivine Le DretCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Catherine RichonCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Ludovic LacroixCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Stéphanie PugetCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Birgit GeoergerCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Gilles VassalCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Arne ÖstmanCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Jacques GrillCNRS UMR 8203 Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (N.T., C.P., F.A., L.G.-R., G.C., L.L.-D., B.G., G.V., J.G.); Functional Genomics Unit, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (C.R.); Translational Research Laboratory and Biobank, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Inserm U981, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Medical Biology and Pathology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (L.L.); Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, Paris XI University, Villejuif, France (B.G., J.G.); Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden (J.P., A.Ö.); Department of Neurosurgery, Necker-Sick Children Hospital, Paris Descartes University, Paris, France (S.P.).
Inserm · FRLaboratoire de Vectorologie et Thérapeutiques Anticancéreuses · FRUniversité Paris-Saclay · FRUniversité Paris Cité · FRCentre National de la Recherche Scientifique · FRDélégation Paris 5 · FRKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPlatelet-derived growth factor receptor A is altered by amplification and/or mutation in diffuse intrinsic pontine glioma (DIPG). We explored in vitro on new DIPG models the efficacy of dasatinib, a multi-tyrosine kinase inhibitor targeting this receptor.

methodsGene expression profiles were generated from 41 DIPGs biopsied at diagnosis and compared with the signature associated with sensitivity/resistance to dasatinib. A panel of 12 new DIPG cell lines were established from biopsy at diagnosis, serially passaged, and characterized by gene expression analyses. Effects of dasatinib (1-10 μM) on proliferation, invasion, and cytotoxicity were determined on 4 of these cell lines using live-cell imaging and flow cytometry assays. Downstream signaling and receptor tyrosine kinases (RTKs) were assessed by western blot and phospho-RTK array. The effect of the combination with the c-Met inhibitor cabozantinib was studied on cellular growth and invasion analyzed by the Chou-Talaly method.

resultsDIPG primary tumors and cell lines exhibited the gene expression signature of sensitivity to dasatinib. Dasatinib reduced proliferation (half-maximal inhibitory concentration = 10-100 nM) and invasion (30%-60% reduction) at 100 nM in 4/4 cultures and induced apoptosis in 1 of 4 DIPG cell lines. Activity of downstream effectors of dasatinib targets including activin receptor 1 was strongly reduced. Since multiple RTKs were activated simultaneously in DIPG cell lines, including c-Met, which can be also amplified in DIPG, the benefit of the combination of dasatinib with cabozantinib was explored for its synergistic effects on proliferation and migration/invasion in these cell lines.

conclusionDasatinib exhibits antitumor effects in vitro that could be increased by the combination with another RTK inhibitor targeting c-Met.

Indexed as

AnilidesAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBrain Stem NeoplasmsCell CycleCell Line, TumorChildChild, PreschoolDasatinibFemaleGliomaHumansMaleNeoplasm InvasivenessPonsProtein Kinase InhibitorsAnilidesAntineoplastic AgentscabozantinibDasatinibProtein Kinase InhibitorsProto-Oncogene Proteins c-metPyridinesReceptor, Platelet-Derived Growth Factor alphaACVR1brainstemPDGFRApreclinical modelSrc

Identifiers

PMID25534822
PMCPMC5654348
OpenAlexW2027446300

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