New therapeutic approaches to metastatic gastroenteropancreatic neuroendocrine tumors: A glimpse into the future

Abstract

Neuroendocrine (NE) gastroenteropancreatic tumors are a heterogeneous group of neoplasias arising from neuroendocrine cells of the embryological gut. Their incidence have increased significantly over the past 3 decades probably due to the improvements in imaging and diagnosis. The recent advances in molecular biology have translated into an expansion of therapeutic approaches to these patients. Somatostatin analogs, which initially were approved for control of hormonal syndromes, have recently been proven to inhibit tumor growth. Several new drugs such as antiangiogenics and others targeting mammalian target of rapamycin pathways have been approved to treat progressive pancreatic neuroendocrine tumors (NETs) although their role in non-pancreatic is still controversial. The treatment of NETs requires a coordinated multidisciplinary approach. The management of localized NETs primarily involves surgical resection followed by surveillance. However, the treatment of unresectable and/or metastatic disease may involve a combination of surgical resection, systemic therapy, and liver-directed therapies with the goal of alleviating symptoms of peptide release and controlling tumor growth. This article will review the current therapeutic strategies for metastatic gastroenteropancreatic NETs and will take a glimpse into the future approaches.

Keywords: Gastroenteropancreatic neuroendocrine tumors, Peptide receptor radionuclide therapy, Somatostatin analogs, Octreotide, Transarterial chemoembolization, Carcinoid syndrome, Setotonin, Chromogranin

Core tip: The management of localized NETs is straight forward, however, the treatment of advanced tumors involves several disciplines and requires a coordinated multidisciplinary approach. Recent advances in molecular biology have expanded the therapeutic arsenal. Somatostatin analogs, initially approved for control of hormonal syndromes, have recently proven to inhibit tumor growth. Several new drugs, antiangiogenics, mTOR inhibitors have been tested with promising results and some of them have already been approved. Several trials are still under way but the future should focus on patient selection, predictive markers, and tolerability improvement as critical aspects to continue advancing.