Page 53 - Read Online

Topic: Neuroendocrine Tumors

Medical therapy for advanced gastro-entero-pancreatic and
bronchopulmonary neuroendocrine tumors

Mariangela Torniai , Silvia Rinaldi , Francesca Morgese , Giulia Ricci , Azzurra Onofri , Christian Grohé ,
1
2
1
1
1
1
Rossana Berardi 1
1 Department of Medical Oncology, Università Politecnica delle Marche, 60100 Ancona, Italy.
2 Department of Respiratory Diseases, Ev. Lungenklinik Berlin, Universitätsmedizin Charite, Lindenberger Weg 27, 13125 Berlin, Germany.
Corresponding Author: Prof. Rossana Berardi, Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria
Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca 71, 60126 Ancona, Italy. E-mail: r.berardi@univpm.it
A B S T R AC T
Neuroendocrine tumors (NETs) represent a spectrum of rare neoplasms arising in different organism sites. Depending on the
site of onset, they also can be distinguished using lab exams (secreting vs. nonsecreting), clinical symptoms (functioning vs.
nonfunctioning), behavioral, morphological characteristics (tumor cells’ architectural growth patterns, mitotic and Ki-67 index,
presence of necrosis), and grade of cellular differentiation. The aim of this review is to focus on the main signaling pathways
targeted by medical treatments of advanced sporadic gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) neuroendocrine
neoplasms. The scientific literature regarding treatment of advanced GEP and BP-NETs has been extensively reviewed using
MEDLINE and PubMed databases, selecting principal and more recent research articles, clinical trials, and updated guidelines.
Somatostatin analogues represent a valid approach to control symptoms in functioning tumors and to inhibit tumor progression
in certain categories on the basis of the typical somatostatin receptor expression observed in NETs. The pathogenesis of NETs
has been the subject of increased interest in recent years. Many driver mutations pathway genes have been identified as important
factors in the carcinogenesis process and, therefore, as potential targets for new anticancer therapies. Activating mutations have
been shown in epidermal growth factor receptor, stem cell factor receptor, platelet-derived growth factor receptor, vascular
endothelial growth factor, basic-fibroblastic growth factor, transforming growth factor, insulin-like growth factor-1, and their
receptors. Effective M-Tor inhibition pathway modulation has led to the approval of drugs in this field such as everolimus. New
drugs and several combination regimens with targeted and newer biological agents are being developed and tested in recently
conducted and ongoing trials.

Key words: Gastrointestinal and bronchopulmonary neuroendocrine tumors; advanced disease; medical treatment; targeted agents

INTRODUCTION Identification of many driver mutations in pathway genes
involved in the pathogenesis of well- and moderately-
Neuroendocrine neoplasms typically occur in differentiated NENs has promoted the development of
gastrointestinal and bronchopulmonary tracts. Gastro- specific targeted therapies. [5-7]
entero-pancreatic neuroendocrine neoplasms (GEP-
NENs) originate from neuroendocrine cells of the Conversely, bronchopulmonary NETs are approximately
gastrointestinal tract and pancreatic islets. [1] 20-25% of all lung malignancies. [8-12] On the basis
of 2004, World Health Organization classification,
Three-tiered grading systems have been proposed pulmonary NETs can be divided into three groups: [13]
for GEP-NENs classification, according to their carcinoid tumors (typical carcinoids/atypical carcinoids)
[2]
morphological features and ki-67 index: neuroendocrine (1-2%), large-cell neuroendocrine (LCNEC) (3%), and
tumors (NETs), involving G1 (ki67 < 3%) and G2 (ki67 ≥
3 and ≤ 20%) neoplasms, and neuroendocrine carcinomas, small-cell carcinomas (SCLC) (15-20%). According to
G3 with ki67 > 20%. Neuroendocrine carcinomas show immunohistochemical markers, these neuroendocrine
worse prognosis, and platinum-based chemotherapy is
currently considered the standard of care. [3,4] This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
the author is credited and the new creations are licensed under the identical
Access this article online terms.
Quick Response Code: For reprints contact: service@oaepublish.com
Website:
www.jcmtjournal.com
How to cite this article: Torniai M, Rinaldi R, Morgese F, Ricci G,
Onofri A, Ghroé C, Berardi R. Medical therapy for advanced gastro-
entero-pancreatic and bronchopulmonary neuroendocrine tumors J
DOI: Cancer Metastasis Treat 2016;2:329-40.
10.20517/2394-4722.2016.47
Received: 28-07-2016; Accepted: 15-08-2016

©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 329