title: The novel kinase inhibitor ponatinib is an effective anti-angiogenic agent against neuroblastoma.
abstract: Background High-risk neuroblastoma has poor outcomes with high rates of relapse despite aggressive treatment, and novel therapies are needed to improve these outcomes. Ponatinib is a multi-tyrosine kinase inhibitor that targets many pathways implicated in neuroblastoma pathogenesis. We hypothesized that ponatinib would be effective against neuroblastoma in preclinical models. Methods We evaluated the effects of ponatinib on survival and migration of human neuroblastoma cells in vitro. Using orthotopic xenograft mouse models of human neuroblastoma, we analyzed tumors treated with ponatinib for growth, gross and histologic appearance, and vascularity. Results Ponatinib treatment of neuroblastoma cells resulted in decreased cell viability and migration in vitro. In mice with orthotopic xenograft neuroblastoma tumors, treatment with ponatinib resulted in decreased growth and vascularity. Conclusions Ponatinib reduces neuroblastoma cell viability in vitro and reduces tumor growth and vascularity in vivo. The antitumor effects of ponatinib suggest its potential as a novel therapeutic agent for neuroblastoma, and further preclinical testing is warranted.
authors: Section of Hematology-Oncology, Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors: Sarah B
authors: SB
authors: Whittle
authors: Department of Pathology, Baylor College of Medicine, Houston, TX, USA.
authors: Kalyani
authors: K
authors: Patel
authors: Section of Hematology-Oncology, Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors: Linna
authors: L
authors: Zhang
authors: Section of Hematology-Oncology, Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.|Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors: Sarah E
authors: SE
authors: Woodfield
authors: Section of Hematology-Oncology, Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors: Michael
authors: M
authors: Du
authors: Section of Hematology-Oncology, Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors: Valeria
authors: V
authors: Smith
authors: Department of Pediatrics, Division of Hematology-Oncology, University of California San Diego School of Medicine, Moores Cancer Center, Room 5311, 3855 Health Sciences Drive, MC 0815, La Jolla, CA, 92093-0815, USA. pzage@ucsd.edu.|Peckham Center for Cancer and Blood Disorders, Rady Children's Hospital, San Diego, CA, USA. pzage@ucsd.edu.
authors: Peter E
authors: PE
authors: Zage
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009447:Neuroblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; C545373:ponatinib
keywords: Angiogenesis; Migration; Neuroblastoma; Ponatinib; Tyrosine kinase