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Topic: Neuroendocrine Tumors

Review of recent advances in medical treatment for neuroendocrine
neoplasms: somatostatin analogs and chemotherapy

Francesca Spada , Monica Valente 2
1
1 Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
2 Medical Oncology and Immunotherapy Division, University Hospital of Siena, viale Bracci 14, 53100 Siena, Italy.
Corresponding Author: Dr. Francesca Spada, Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of
Oncology, Via Ripamonti 435, 20141 Milan, Italy. E-mail: francesca.spada@ieo.it
Dr. Francesca Spada has been actively involved in clinical and research activity of NETs at IEO (Milan) since 2009, where
she is currently quality coordinator of IEO ENETS Center of Excellence for GEP NETs. She is involved in educational program
in NETs particularly as a secretary of NET Italian Guidelines. She is member of the some scientific societies: AIOM, ItaNET,
ESMO, ENETS, NANETS.

A B S T R AC T
Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours often producing high levels of hormones and
causing symptoms. There are a number of different types of NENs. They usually arise as advanced and low/intermediate grade
only in a minority of cases, as high grade. Treatment depends on which type and may include surgery, interventional radiology,
and systemic treatment, including chemotherapy, somatostatin analogs, interferon α2b, peptide receptor radionuclide therapy, and
only for pancreatic neuroendocrine tumors, molecular targeted agents, including everolimus and sunitinib. The aim of the article
is to review the medical approaches with somatostatin analogs and chemotherapy. The treatment of NENs is mainly based on their
biological characteristics of aggressiveness and functional features, such as symptoms and endocrine markers.

Key words: Neuroendocrine neoplasms; somatostatin analogs; chemotherapy; peptide receptor radionuclide therapy; molecular
targeted agents

INTRODUCTION In recent years, strong evidence has emerged of an
antiproliferative effect of SSAs on NENs, thought to occur
Neuroendocrine neoplasms (NENs) are a group of via direct and indirect mechanisms. The direct mode of
[11]
tumours arising from various different epithelial cells action involves interaction with somatostatin receptors
with patterns of neuroendocrine differentiation, usually on tumor cells leading to activation of phosphotyrosine
[12]
from the gastrointestinal tract and the bronchopulmonary phosphatases and modulation of the mitogen-activated
[13]
system. The World Health Organization (WHO) protein kinase signaling pathway. The indirect
[1]
antiproliferative effect occurs through inhibition of
2010 classification distinguishes this class of diseases expression of growth factors, such as insulin-like growth
between well differentiated and poorly differentiated factor and vascular endothelial growth factor. Activities
[14]
neuroendocrine carcinomas. The choise of appropriate of SSAs are mediated by interaction of somatostatin
[2]
treatment depends on their biological and morphological with a series of five receptors (SSTRs) encoded by five
characteristics, functional status, and disease stage. Surgery different genes belonging to the class of receptors linked
is the best option for resectable tumours, whereas in cases to transmembrane G-proteins, able to inhibit cAMP.
of locoregional unresectable and metastatic disease, Therapeutic activity is achieved through interaction
therapeutic options include somatostatin analogs (SSAs), with two of the five SSTRs and, more precisely, with
[3]
[15]
inhibitors of the mammalian target of rapamycin, [4-6] subtypes 2 and 5, for which there is the highest affinity.
receptor tyrosine kinase inhibitors, [7,8] chemotherapy, and
[9]
pepetide receptor radionuclide therapy (PRRT). [10] This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
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How to cite this article: Spada F, Valente M. Review of recents
advances in medical treatment for neuroendocrine neoplasms:
somatostatin analogs and chemotherapy. J Cancer Metasta Treat
DOI: 2016;2:313-20.
10.20517/2394-4722.2016.38
Received: 20-06-2016; Accepted: 18-07-2016
©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 313