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Oncological management of advanced neuroendocrine tumours (Review)
1Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznań 60-355, Poland.
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.
Insights
Managing gastroenteropancreatic neuroendocrine tumors (GEP-NETs) requires a multidisciplinary approach with evolving therapies. Novel agents targeting angiogenesis and mTOR show promise in suppressing GEP-NET growth and metastasis.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) management is complex, necessitating a multidisciplinary strategy.
- Recent advancements offer new therapeutic avenues, including biotherapy, chemotherapy, and targeted agents.
Purpose of the Study:
- To review current and emerging therapeutic options for GEP-NETs.
- To discuss the role of angiogenesis inhibitors and mTOR inhibitors in GEP-NET treatment.
Main Methods:
- Review of recent clinical data and preclinical findings on GEP-NET therapies.
- Analysis of mechanisms of action for somatostatin analogues, interferon, anti-VEGF agents, and mTOR inhibitors.
Main Results:
- Somatostatin analogues (SSAs) and interferon exhibit antisecretory, immunomodulatory, and antiproliferative effects.
- Anti-VEGF monoclonal antibodies inhibit tumor growth and metastasis in preclinical models.
- mTOR inhibition suppresses neuroendocrine tumor growth.
Conclusions:
- Therapeutic decisions for GEP-NETs must be individualized based on disease severity and patient factors.
- Targeting angiogenesis and the mTOR pathway represents a promising strategy for GEP-NET management.
