Neuroendocrine tumors:current therapies,notch signaling,and cancer stem cells

Neuroendocrine tumors(NETs)encompass a broad spectrum of malignancies all derived from neuroendocrine cell lineage,affecting many different organs including the gastrointestinal(GI)tract,the endocrine pancreas,the thyroid,the skin and the respiratory tract.These tumors as a group are very heterogeneous,with varying characteristics attributed to each tissue of origin and tumor subtype.The pathogenesis of the different subtypes of NETs is not fully understood,but recent studies suggest the Notch signaling pathway may be dysregulated in these tumors either by under or overexpression of Notch receptors and/or ligands,or by disruption of pathway functionality through other means.Notch receptors can function as tumor suppressors in some cellular contexts and oncogenes in others which may,in part,account for the wide range of phenotypes present in NETs.Cancer stem cells are present in these tumors and may be responsible for the high rate of chemotherapy resistance,recurrence and metastasis.The heterogeneity of NETs suggests that to fully understand the role of Notch signaling and the therapeutic implications thereof,a comprehensive and systematic analysis of Notch expression and function across all NET subtypes is required.Here we outline the current knowledge base with respect to current therapies and Notch signaling in neuroendocrine tumors of the lung,skin,thyroid,GI tract and endocrine pancreas.