Oncological management of advanced neuroendocrine tumours (Review)

Abstract

The oncological principles of managing patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) depends on a number of factors and requires a multidisciplinary approach. Recent data have provided additional therapeutic options, including biotherapy, traditional chemotherapy and novel targeted agents. Somatostatin analogues (SSAs) inhibit multiple cellular functions, including secretion, motility and proliferation. Interferon appears to act through several mechanisms, with antisecretory effects, immunomodulatory effects and antiproliferative functions, the latter inhibiting direct growth or attenuating angiogenesis. Opinions on when to commence chemotherapy for well differentiated GEP-NETs varies among experts. In previous years, reserving chemotherapy for patients with progressive disease (well differentiated, inoperable and/or metastatic GEP-NETs) was reasonably well argued for. Most well differentiated endocrine tumours are richly vascular and many express vascular endothelial growth factor (VEGF) receptors. In a xenograft model of a human carcinoid, treatment with an anti-VEGF monoclonal antibody was revealed to inhibit tumour growth and metastasis. As the role of angiogenesis and hypoxic-associated factors appears to be associated with tumour aggressiveness, strategies using agents which target angiogenesis have been developed. Mammalian target of rapamycin (mTOR) is a conserved serine-threonine kinase that regulates the cell cycle and metabolism in response to environmental factors. In addition, mTOR inhibition suppression was demonstrated to suppress NET growth. Each patient requires an individual approach to the choice of therapy, which should be selected depending on the severity of disease.