Meeting report-3rd Neuroblastoma Research Symposium, Liverpool, 6-7th November, 2013

Abstract

Neuroblastoma is an embryonal malignancy of the developing neural crest. Despite improvements in treatment, prognoses remain dire for patients with high-risk disease. Interest in this enigmatic cancer has led to a rapidly changing research landscape and we report on the recent advances in four themes that were discussed at the 3rd Neuroblastoma Research Symposium: (1) The epigenetic signature of neuroblastoma and the epigenetic control of tumour development, (2) novel approaches to targeting MYCN, (3) valuable in vivo modelling and (4) improving differentiation therapies based on a knowledge of normal sympathetic neuron development. Through lively discussion, the development of combined therapies with synergistic effects for which we have a good mechanistic understanding emerged as offering greatest promise. Drug synergies enhance efficacy but also specificity, the latter crucial for reducing long-term side effects in young children.

Neuroblastoma patient‐derived orthotopic xenografts retain metastatic patterns and geno‐ and phenotypes of patient tumours

“…5 It has become increasingly clear that tumour cells cultured in vitro can develop aberrant and irreversible genetic and phenotypic changes not consistent with the properties of the original patient tumour. 10 In addition, as shown here and previously reported, 5,11 cell line-derived orthotopic neuroblastoma xenografts often lack substantial spontaneous metastasis to bone marrow. Although results from cell line-derived studies have been valuable, generation of neuroblastoma patientderived xenografts (PDXs) by implantation of viable tumour explants from cancer patients is an alternative approach to better maintain patient-derived tumour cell features.…”

“…In the SK‐N‐BE(2)c cell model used here, several aberrant features not typical for the clinical disease were found, most importantly lack of bone marrow involvement. Indeed, one obstacle when studying neuroblastoma metastasis has been the scarcity of xenograft models that retain the metastatic pattern of the disease . Here, we show that orthotopic neuroblastoma PDXs are reliable models for human neuroblastoma bone marrow metastasis.…”

“…Indeed, one obstacle when studying neuroblastoma metastasis has been the scarcity of xenograft models that retain the metastatic pattern of the disease. 11 Here, we show that orthotopic neuroblastoma PDXs are reliable models for human neuroblastoma bone marrow metastasis. The presence of liver and lung metastasis in the PDX models are also consistent with the findings of liver and lung micrometastases in more than half of neuroblastoma patients analysed by immunohistochemistry postmortem.…”