Combining SOS1 and MEK Inhibitors in a Murine Model of Plexiform Neurofibroma Results in Tumor Shrinkage.

Animals Mice Disease Models, Animal Extracellular Signal-Regulated MAP Kinases / metabolism Mitogen-Activated Protein Kinase Kinases Neurofibroma / drug therapy Neurofibroma, Plexiform / drug therapy Neurofibromatosis 1 / drug therapy Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins p21(ras) / metabolism Tumor Microenvironment SOS1 Protein / metabolism

Journal

The Journal of pharmacology and experimental therapeutics
ISSN: 1521-0103
Titre abrégé: J Pharmacol Exp Ther
Pays: United States
ID NLM: 0376362

Informations de publication

Date de publication:
05 2023
Historique:
received: 01 09 2022
accepted: 13 02 2023
medline: 12 4 2023
pubmed: 28 2 2023
entrez: 27 2 2023
Statut: ppublish

Résumé

Individuals with neurofibromatosis type 1 develop rat sarcoma virus (RAS)-mitogen-activated protein kinase-mitogen-activated and extracellular signal-regulated kinase (RAS-MAPK-MEK)-driven nerve tumors called neurofibromas. Although MEK inhibitors transiently reduce volumes of most plexiform neurofibromas in mouse models and in neurofibromatosis type 1 (NF1) patients, therapies that increase the efficacy of MEK inhibitors are needed. BI-3406 is a small molecule that prevents Son of Sevenless (SOS)1 interaction with Kirsten rat sarcoma viral oncoprotein (KRAS)-GDP, interfering with the RAS-MAPK cascade upstream of MEK. Single agent SOS1 inhibition had no significant effect in the DhhCre;Nf1

Identifiants

DOI: 10.1124/jpet.122.001431 PMID: 36849412 PMC: PMC10108440
pubmed: 36849412
pii: jpet.122.001431
doi: 10.1124/jpet.122.001431
pmc: PMC10108440
doi:

Substances chimiques

Extracellular Signal-Regulated MAP Kinases EC 2.7.11.24
Mitogen-Activated Protein Kinase Kinases EC 2.7.12.2
Protein Kinase Inhibitors 0
Proto-Oncogene Proteins p21(ras) EC 3.6.5.2
SOS1 Protein 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106-116

Informations de copyright

U.S. Government work not protected by U.S. copyright.

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Auteurs

Mark Jackson (M)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Niousha Ahmari (N)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Jianqiang Wu (J)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).
ORCID: 0000-0002-4239-5659

Tilat A Rizvi (TA)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Elizabeth Fugate (E)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Mi-Ok Kim (MO)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Eva Dombi (E)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Heribert Arnhof (H)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Guido Boehmelt (G)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Matthias J Düchs (MJ)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Clive J Long (CJ)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Udo Maier (U)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Francesca Trapani (F)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.).

Marco H Hofmann (MH)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.) nancy.ratner@cchmc.org marco.hofmann@boehringer-ingelheim.com.

Nancy Ratner (N)

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute (M.J., N.A., J.W., T.A.R., N.R.) and Department of Radiology (E.F.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (M.-O.K.); Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland (E.D.); Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria (H.A., G.B., F.T., M.H.H.); Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany (M.J.D., C.J.L., U.M.); and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio (J.W., N.R.) nancy.ratner@cchmc.org marco.hofmann@boehringer-ingelheim.com.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › Extracellular Signal-Regulated MAP Kinases › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › Mitogen-Activated Protein Kinase Kinases › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Maladies du système nerveux › Maladies neuromusculaires › Neuropathies périphériques › Tumeurs du système nerveux périphérique › Tumeurs des gaines nerveuses › Neurofibrome › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Maladies du système nerveux › Maladies neuromusculaires › Neuropathies périphériques › Tumeurs du système nerveux périphérique › Tumeurs des gaines nerveuses › Neurofibrome › Neurofibrome plexiforme › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Syndromes néoplasiques héréditaires › Neurofibromatoses › Neurofibromatose de type 1 › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéines kinases › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes p21(ras) › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Combining SOS1 and MEK Inhibitors in a Murine...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Régulateurs des protéines G › Facteurs d'échange de nucléotides guanyliques › Facteur ras d'échange de nucléotides guanyliques › Protéines Son of sevenless › Protéine SOS1 › Combining SOS1 and MEK Inhibitors in a Murine...