New molecular aspects in the diagnosis and therapy of neuroendocrine tumors of the gastroenteropancreatic system.

Abstract

The nature and biology of neuroendocrine cells and of tumors derived therefrom have been the subject of intense research using cell biological and molecular approaches. Diagnostic procedures for establishing the diagnosis of a neuroendocrine tumor have been improved through the development of new serological markers and imaging procedures. Histopathological diagnosis has been refined by the introduction of a broad spectrum of marker proteins for different subtypes of neuroendocrine neoplasms. The high receptor specificity of somatostatin analogues such as octreotide or lanreotide has made these drugs valuable tools in diagnosis and therapy, and some of the achievements made as well as future directions are reviewed in this article. Another substance in use for therapy of neuroendocrine tumors is interferon-a, whose signal transduction mechanism has been investigated considerably during the past several years. In addition to biotherapy with somatostatin analogues and/or interferon-a, chemotherapy is an accepted strategy in the treatment of advanced neuroendocrine tumor disease derived from the foregut. In this context, streptozotocin has caught some attention due to its somewhat selective toxicity against neuroendocrine tumor cells. Some recent studies on the role of the glucose transporter isoform GLUT2 may provide insight into streptozotocin's action. The multiple endocrine neoplasia type-1 gene has recently been cloned, sequenced and identified as a gene potentially involved in the development of the familial cancer syndrome of multiple endocrine neoplasia type 1 (MEN-1). Mutations of this putative tumor suppressor gene have been described, and the abundance of mutations in MEN-1-related tumors as well as sporadic neuroendocrine tumors at MEN-1 locations have been demonstrated. Whether determination of MEN-1 mutations will be valuable for clinical routine is under investigation.