title: BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells.
abstract: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment.
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.|Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), 90050-170, Porto Alegre, RS, Brazil.
authors.forename: Amanda
authors.initials: A
authors.lastname: Thomaz
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.|Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), 90050-170, Porto Alegre, RS, Brazil.
authors.forename: Mariane
authors.initials: M
authors.lastname: Jaeger
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.|Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), 90050-170, Porto Alegre, RS, Brazil.
authors.forename: Marienela
authors.initials: M
authors.lastname: Buendia
authors.affiliation: Laboratory of Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 21040-360, Rio de Janeiro, RJ, Brazil.
authors.forename: Victorio
authors.initials: V
authors.lastname: Bambini-Junior
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.|Department of Pediatrics, Faculty of Medicine, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Lauro José
authors.initials: LJ
authors.lastname: Gregianin
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.|Children's Cancer Institute (ICI), 90420-140, Porto Alegre, RS, Brazil.
authors.forename: Algemir Lunardi
authors.initials: AL
authors.lastname: Brunetto
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.|Children's Cancer Institute (ICI), 90420-140, Porto Alegre, RS, Brazil.
authors.forename: André T
authors.initials: AT
authors.lastname: Brunetto
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.|Children's Cancer Institute (ICI), 90420-140, Porto Alegre, RS, Brazil.
authors.forename: Caroline Brunetto
authors.initials: CB
authors.lastname: de Farias
authors.affiliation: Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil. rroesler@terra.com.br.|Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), 90050-170, Porto Alegre, RS, Brazil. rroesler@terra.com.br.|Children's Cancer Institute (ICI), 90420-140, Porto Alegre, RS, Brazil. rroesler@terra.com.br.
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020813:Receptor, trkB; D015398:Signal Transduction
chemical_list: C559317:ANA 12 compound; D000970:Antineoplastic Agents; D001381:Azepines; D001549:Benzamides; D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
keywords: Brain tumor; Brain-derived neurotrophic factor; Childhood cancer; Medulloblastoma; TrkB