Neuroendocrine tumors: From bench to bed - 25 years experience and the future
Neuroendocrine tumors of the GI-tract have attained increased attention during the last decades. The incidence of these rare neoplasms is about 2.5-4.0 per 100.000 per year.
The most significant developments within the management of neuroendocrine GI-tumors have been in the areas of histopathology, tumor markers, localisation procedures and treatment. A new WHO-classification system has emerged which not only classify the tumor as neuroendocrine, but also indicate the degree of malignancy [Ki67 (MIB-1)]. Chromogranin A described in the 1960:s has now been recognized as the most important general tumor marker for NE-tumors. Somatostatin receptor scintigraphy is very important for staging of the disease. PET-scanning with C11-5HTP has been the most sensitive method to detect very small tumors. Cytotoxic treatment has been the gold standard for highly malignant neuroendocrine GI-tumors with high proliferation capacity. However, biological treatment (somatostatin analogues and alpha interferons) has been the real break-through in the management a functioning low proliferating GI-tumors. Tumor targeted radioactive treatment is nowadays somatostatin analogue based, using 90Yttrium DOTA-Octretotide or 177Lu DOTA-Octreotate. In the future the diagnosis of neuroendocrine GI-tumors will be made by micro-arrays and proteomics. The new treatment will be based on molecular profiling and each tumor will be analyzed for different growth factors, receptors, cytokines and signal transduction enzymes. Neuroendocrine GI-tumors express a lot of tyrosine kinase receptors, in the future new agents targeting these receptors will be attempted as well as Rapamycin, targeting the m-tor signal transduction pathway. New somatostatin analogues will come into clinical practice. SOM230, with strong inhibition of IGF-1, which is an important growth factor in many neuroendocrine GI-tumors is in phase II studies. The tumor targeted radioactive treatment will be furthermore improved with combinations of 90Yttrium DOTA-Octreotide and 177Lu DOTA-Octreotate.