DISORDERED DIFFERENTIATION AS A TARGET FOR NOVEL APPROACHES TO THE TREATMENT OF NEUROBLASTOMA

Some childhood malignant neoplasms are thought to arise in embryonic t issues. These tumors present unique opportunities for studying the mat uration of specific cellular lineages and examining the possible role of alterations in the regulation of differentiation in tumor developme nt. Several features of neuroblastoma, a tumor thought to arise in cel ls originating in the embryonic neural crest, suggest that it may be p articularly useful in this regard. The identification of a series of m arkers that characterize the various cell types of the peripheral nerv ous system that are detectable in neuroblastoma tumor tissues has made it possible to recognize that the cells of neuroblastoma tumor cell l ines and tissues correspond to specific stages of adrenal gland develo pment. Experiments directed at understanding the cellular signals by w hich 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 cyto toxic therapies than tumors corresponding to other stages.