Neuroblastoma is the most common and deadly solid tumor in children. This tumor accounts for 8-10% of the cancers and 15% of the deaths from cancer in childhood. Although a third of children are diagnosed under the age of 1 year, the majority of children are diagnosed between 1 and 10 years of age, and most of these have metastatic disease and will die from tumor progression. The goal of this Program Project Grant entitled """"""""Neuroblastoma Biology and Therapy"""""""" is to investigate specific biological pathways critical to neuroblastoma tumorigenesis and progression and to develop novel approaches to treatment that are aimed at these pathways. This program is organized into 4 projects and 4 Cores: Project 1. P75 and Trk in Neuroblastoma Differentiation and Death (Garrett Brodeur, Leader). Project 2. Antiangiogenic Strategies for Neuroblastoma Therapy (John Maris, Leader) Project 3. Deregulated Apoptosis in MYCN Amplified Neuroblastomas (Michael Hogarty, Leader) Project 4. Integration of Retinoids with Cytotoxic Agents in Neuroblastoma (Peter Adamson, Leader). Core . Animal Model and Pathology Core (John Maris, Core Director; Bruce Pawel, Co-Director) Core . Biostatistics and Bioinformatics Core (Avital Cnaan, Core Director; Eric Rappaport, Co-Director) Core . Pharmacokinetics Core (Peter Adamson, Core Director) There is increasing interest in novel approaches to cancer treatment with tyrosine kinase inhibitors, angiogenesis inhibitors, cell death-promoting agents and retinoids. We plan to develop novel therapies that are biologically based and likely to have clinical efficacy. The successful completion of these studies should identify novel agents and combinations of agents aimed at important growth, differentiation and cell death pathways that should be very effective and far less toxic than conventional therapy. We anticipate moving these treatment approaches rapidly into clinical trials. Furthermore, treatment strategies developed against neuroblastoma may be useful against other tumors in children and adults that are rely on the biological pathways and are affected by these agents.
| Norris, Robin E; Nguyen, Vu T; Adamson, Peter C (2014) Evaluation of the retinoids with cisplatin and vincristine in xenograft models of neuroblastoma. J Pediatr Hematol Oncol 36:e23-7 |
| Laetsch, T W; Liu, X; Vu, A et al. (2014) Multiple components of the spliceosome regulate Mcl1 activity in neuroblastoma. Cell Death Dis 5:e1072 |
| Boiani, Mariana; Daniel, Cristina; Liu, Xueyuan et al. (2013) The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. J Biol Chem 288:6980-90 |
| Zhi, Wei; Minturn, Jane; Rappaport, Eric et al. (2013) Network-based analysis of multivariate gene expression data. Methods Mol Biol 972:121-39 |
| Goldsmith, Kelly C; Gross, Michelle; Peirce, Susan et al. (2012) Mitochondrial Bcl-2 family dynamics define therapy response and resistance in neuroblastoma. Cancer Res 72:2565-77 |
| Iyer, Radhika; Varela, Carly R; Minturn, Jane E et al. (2012) AZ64 inhibits TrkB and enhances the efficacy of chemotherapy and local radiation in neuroblastoma xenografts. Cancer Chemother Pharmacol 70:477-86 |
| Qing, Guoliang; Li, Bo; Vu, Annette et al. (2012) ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 22:631-44 |
| Light, Jennifer E; Koyama, Hiroshi; Minturn, Jane E et al. (2012) Clinical significance of NTRK family gene expression in neuroblastomas. Pediatr Blood Cancer 59:226-32 |
| Ho, Ruth; Minturn, Jane E; Simpson, Anisha M et al. (2011) The effect of P75 on Trk receptors in neuroblastomas. Cancer Lett 305:76-85 |
| Norris, Robin E; Minturn, Jane E; Brodeur, Garrett M et al. (2011) Preclinical evaluation of lestaurtinib (CEP-701) in combination with retinoids for neuroblastoma. Cancer Chemother Pharmacol 68:1469-75 |
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