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Disordered differentiation as a target for novel approaches to the treatment of neuroblastoma

Some childhood malignant neoplasms are thought to arise in embryonic tissues. These tumors present unique opportunities for studying the maturation of specific cellular lineages and examining the possible role of alterations in the regulation of differentiation in tumor development. Several features of neuroblastoma, a tumor thought to arise in cells originating in the embryonic neural crest, suggest that it may be particularly useful in this regard. The identification of a series of markers that characterize the various cell types of the peripheral nervous system that are detectable in neuroblastoma tumor tissues has made it possible to recognize that the cells of neuroblastoma tumor cell lines and tissues correspond to specific stages of adrenal gland development. Experiments directed at understanding the cellular signals by which neural crest cell maturation is mediated may provide insights of therapeutic import because neuroblastoma tumors corresponding to some stages of differentiation respond very differently to nonspecific cytotoxic therapies than tumors corresponding to other stages.