Investigational drugs in phase II clinical trials for the treatment of neuroblastoma.

Neuroblastoma (NB) is an embryonal tumor originating from undifferentiated neural crest cell, highly heterogeneous ranging from spontaneous regression to progression despite multimodal treatments. Approximately, 20% of patients are refractory to frontline therapy and 50% will relapse/progress after an initial response. The overall five year survival for high-risk neuroblastoma ranges from 35-45%. Despite enhanced understanding of NB biology and the addition of myeloablative chemotherapy, isotretinoin and immunotherapy, survival for high risk NB remains less than 50%. Areas covered: This review summarizes and gives a critical overview of phase II trials investigating therapies for relapsed-refractory and high risk neuroblastoma. Expert opinion: Several novel molecules have been developed and are currently under investigation for the treatment of NB. The trend of novel targeted agents is one towards individualized, tailored therapy, based on the molecular and biological differences that characterize tumors that seem similar based solely on histological analysis. The task of developing new molecules is particularly difficult for NB, given the recurrent development of new patterns of drug resistance. However, even if current research is focused towards identifying the best treatments for each children and young adult with a NB defined disease, a deeper knowledge of the molecular biology and genetics is needed.