Preclinical models of pediatric solid tumors (neuroblastoma) and their use in drug discovery

Curr Protoc Pharmacol. 2011 Mar:Chapter 14:Unit 14.17. doi: 10.1002/0471141755.ph1417s52.

Abstract

Neuroblastoma is the most common pediatric abdominal solid tumor. This aggressive embryonal malignancy of neural crest origin has a peak age of onset of 22 months, and accounts for ~11% of all pediatric cancers and 15% of all pediatric cancer deaths. With current treatment protocols, including high-dose chemotherapy with autologous stem cell transplantation, radiation, and surgery, ~80% of high-risk patients go into remission, although the majority relapse and succumb to therapy-resistant tumors. Long-term survival rates (>5 years) are <50%. Mouse models of neuroblastoma provide clinically relevant tools for studying the growth and metastasis of this aggressive malignancy, and for testing the efficacy of potentially novel therapeutics in vivo. This unit describes an orthotopic murine model of neuroblastoma using cultured human cells that closely mimics the clinical condition in terms of the bulky intra-abdominal tumors and other aspects of metastatic disease. Also described are methods for in vivo imaging and monitoring of tumor growth, and procedures for necropsy and tumor preservation for pathological analysis.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Child
  • Disease Models, Animal*
  • Drug Discovery / methods*
  • Humans
  • Infant
  • Luminescence
  • Mice
  • Neuroblastoma / diagnosis
  • Neuroblastoma / drug therapy
  • Neuroblastoma / pathology*
  • Tumor Cells, Cultured
  • Whole Body Imaging / methods

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab