Pediatric Oncology Research Unit
Solid tumours in children represent a group of tumours (central nervous system tumours, neuroblastomas, soft tissue sarcomas, Wilms’tumours) with specific biology, genetics and environmental features that clearly set them apart from adult tumours.
Neuroblastoma is the most typical early childhood tumour and also common extra cranial solid cancer in children originating from neural crest-derived sympathetic nervous system (SNS) precursors.
Despite many advances during the past decades, neuroblastoma has remained an enigmatic challenge to clinical and basic scientists. Amplification of the MYCN proto-oncogene was the first segmental genetic alteration to be associated to tumour progression and unfavourable clinical outcome. Research has since then focused on the search for additional genetic markers. It has emerged that neuroblastoma cells present alterations at multiple genetic loci, but as yet, the primary genetic alterations responsible for tumour development remain elusive.
The disease can be considered as resulting from an aberrant development of the SNS, particularly in the mechanisms which control balance between cell proliferation and differentiation. In addition, lack of responsiveness to apoptotic signals, and the degree of dependence on extrinsic growth/trophic factors are other areas in which mutation may allow evasion of the normal SNS developmental program.
Our group has been involved in Neuroblastoma Research since two decades. We have provided clues to the typical phenotypic properties of neuroblastoma with specific markers expression (GD2, HNK-1), and typical loss of ubiquitous HLA class I, CD44, surface molecules, death receptors (Fas), and pro-apoptotic molecules (caspase-8/10). We have shown that as a result, these tumours were able to escape immunosurveillance or multiple apoptotic signals and thus progress in uncontrolled way due to multiple altered signalling pathways. Our work on neuroblastoma is currently orientated in four distinct themes:
- Mechanisms of resistance in apoptosis induction
- Role of chemokine receptors axis in tumours growth and dissemination
- Multi-drug resistance (MDR)
- Identification of tumour initiating cells (TIC)
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