Progress in treatment and risk stratification of neuroblastoma: impact on future clinical and basic research

Abstract

Close international collaboration between pediatric oncologists has led to marked improvements in the cure of patients, seen as a long-term overall survival rate of about 80%. Despite this progress, neuroblastoma remains a challenging disease for both clinicians and researchers. Major clinical problems include lack of acceptable cure rates in high-risk neuroblastoma and potential overtreatment of subsets of patients at low and intermediate risk of the disease. Many years of intensive international cooperation have recently led to a promising joint effort to further improve risk classification for treatment stratification, the new International Neuroblastoma Risk Group Classification System. This approach will facilitate comparison of the results of clinical trials performed by different international collaborative groups. This, in turn, should accelerate refinement of risk stratification and thereby aid selection of appropriate therapies for individual patients. To be able to identify new therapeutic modalities, it will be necessary to elucidate the pathogenesis of the different subtypes of neuroblastoma. Basic and translational research have provided new tools for molecular characterization of blood and tumor samples including high-throughput technologies for analysis of DNA, mRNAs, microRNAs and other non-coding RNAs, as well as proteins and epigenetic markers. Most of these studies are array-based in design. In neuroblastoma research they aim to refine risk group stratification through incorporation of molecular tumor fingerprints and also to enable personalized treatment modalities by describing the underlying pathogenesis and aberrant signaling pathways in individual tumors. To make optimal use of these new technologies for the benefit of the patient, it is crucial to have a systematic and detailed documentation of both clinical and molecular data from diagnosis through treatment to follow-up. Close collaboration between clinicians and basic scientists will provide access to combined clinical and molecular data sets and will create more efficient steps in response to the remaining treatment challenges. This review describes the current efforts and trends in neuroblastoma research from a clinical perspective in order to highlight the urgent clinical problems we must address together with basic researchers.