Editorial [Hot Topic:Treatment of Neuroblastoma: From Cellular to Molecular Therapy (Executive Editor: Gian Paolo Tonini)]

Neuroblastic Tumors is a group of pediatric cancers with a high incidence in the preschool age. Neuroblastic Tumors are classified in several histological categories but neuroblastoma, composed by undifferentiated cell without stromal tissue is the most aggressive disseminated tumor occurring in patients over 18 months of age. Neuroblastoma attracted the attention of scientists since the middle century because metastatic tumor in infants very often regressed while in older patients was very aggressive. In 1973 Biedler and coworkers established cell cultures from human metastatic neuroblastoma tissues and opened a new era in biological and pharmacological study of this cancer. Afterwards several human cell lines were established and transplanted in mice giving the opportunity to study the effect of drug both in vitro and in vivo. Meantime patients were carefully managed and risk of relapse was assessed by age, extension of disease, biological and genomic factors. Furthermore, specimens of primary tumors were accurately stored and biological repositories go a long way towards studying biological and molecular aspects of neuroblastoma. Although the great advances in tumor biology, patients with metastatic stage 4 disease still have the worst prognosis. From several years the Children's Oncology Group (COG) and Societe Internationale Oncologie Pediatrique Europeenne Neuroblastoma (SIOPEN) have reduced therapy for children with localized disease in which surgery is the most effective approach to improve patient survival. Risk of patients with localized disease is increased by the presence of MYCN gene amplification in tumor cells and these patients receive chemotherapy. Conversely, high-dose therapy and retinoic acid administered after bone marrow ablation are used for patients with advanced disease. Unfortunately, about 6% of patients with localized tumors and more than 50% of patients with disseminated aggressive tumor have a disease progression and died. So, new therapeutic approaches are urgently necessary. Meanwhile, COG and SIOPEN groups are working to define new genetic/biological markers in order to perform a therapy more precise in children with neuroblastoma. Information on the MYCN copy number, the most important oncogene associated with tumor progression in neuroblastoma, has gained central importance in decision- making process concerning patients' treatment. The absence or presence of MYCN amplification represents frequently the only criterion which prompts clinicians to choose between a ‘wait and see strategy’ or an aggressive cytotoxic treatment.