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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2020; 26(28): 4036-4054
Published online Jul 28, 2020. doi: 10.3748/wjg.v26.i28.4036
Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations
Gabriel Benyomo Mpilla, Philip Agop Philip, Bassel El-Rayes, Asfar Sohail Azmi
Gabriel Benyomo Mpilla, Philip Agop Philip, Asfar Sohail Azmi, Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, United States
Bassel El-Rayes, Department of Hematology Oncology, Emory Winship Institute, Atlanta, GA 30322, United States
Author contributions: Gabriel BM, Philip AP, El-Rayes B and Asfar SA contributed to concept design, literature search, writing and editing the manuscript.
Supported by NIH, No. R01 CA240607-01A1; and SKY Foundation Inc.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Asfar Sohail Azmi, PhD, Associate Professor, Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, HWCRC 732, Detroit, MI 48201, United States. azmia@karmanos.org
Received: April 21, 2020
Peer-review started: April 31, 2020
First decision: July 8, 2020
Revised: June 10, 2020
Accepted: July 16, 2020
Article in press: July 16, 2020
Published online: July 28, 2020
Processing time: 97 Days and 19.3 Hours
Abstract

Pancreatic neuroendocrine tumors (PNETs) are known to be the second most common epithelial malignancy of the pancreas. PNETs can be listed among the slowest growing as well as the fastest growing human cancers. The prevalence of PNETs is deceptively low; however, its incidence has significantly increased over the past decades. According to the American Cancer Society’s estimate, about 4032 (> 7% of all pancreatic malignancies) individuals will be diagnosed with PNETs in 2020. PNETs often cause severe morbidity due to excessive secretion of hormones (such as serotonin) and/or overall tumor mass. Patients can live for many years (except for those patients with poorly differentiated G3 neuroendocrine tumors); thus, the prevalence of the tumors that is the number of patients actually dealing with the disease at any given time is fairly high because the survival is much longer than pancreatic ductal adenocarcinoma. Due to significant heterogeneity, the management of PNETs is very complex and remains an unmet clinical challenge. In terms of research studies, modest improvements have been made over the past decades in the identification of potential oncogenic drivers in order to enhance the quality of life and increase survival for this growing population of patients. Unfortunately, the majority of systematic therapies approved for the management of advanced stage PNETs lack objective response or at most result in modest benefits in survival. In this review, we aim to discuss the broad challenges associated with the management and the study of PNETs.

Keywords: Pancreatic neuroendocrine tumors; Gastroenteropancreatic neuroendocrine tumors; Management; Limitation; Novel Agents; Emerging targets

Core tip: Pancreatic Neuroendocrine Tumors (PNETs) can cause severe morbidity due to excessive hormones production and overall tumor mass. The majority of approved therapeutic options in PNETs lack objective response suggesting that there is still a void in the understanding of the biology of this neoplasia. With the rising incidence and the underestimated prevalence of PNETs in the United States, it is paramount to discuss the challenges associated with the study and the management of this intractable disease for better patient outcomes. In this paper we elaborate on the comprehensive challenges and discuss novel and emerging therapeutic target in PNETs.