Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2021; 27(24): 3568-3580
Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3568
Room for improvement in the treatment of pancreatic cancer: Novel opportunities from gene targeted therapy
Michail Galanopoulos, Aris Doukatas, Filippos Gkeros, Nikos Viazis, Christos Liatsos
Michail Galanopoulos, Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge CB2 0QQ, United Kingdom
Aris Doukatas, Department of Pharmacy, National and Kapodistrian University of Athens, Athens GR 15772, Greece
Filippos Gkeros, Nikos Viazis, Department of Gastroenterology, Evangelismos, Ophthalmiatreion Athinon and Polyclinic Hospitals, Athens 10676, Greece
Christos Liatsos, Department of Gastroenterology, 401 General Military Hospital, Athens 11525, Greece
Author contributions: Galanopoulos M designed the review; Galanopoulos M, Doukatas A and Gkeros F analyzed and interpreted the data; Galanopoulos M, Viazis N and Doukatas A drafted the manuscript; Liatsos C critically revised the paper; all authors have read and approved the final manuscript.
Conflict-of-interest statement: Nothing to declare.
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:
Corresponding author: Michail Galanopoulos, FEBG, MD, PhD, Doctor, Department of Gastroenterology, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom.
Received: February 16, 2021
Peer-review started: February 16, 2021
First decision: March 28, 2021
Revised: April 11, 2021
Accepted: May 22, 2021
Article in press: May 22, 2021
Published online: June 28, 2021

Pancreatic cancer is one of the highest and in fact, unchanged mortality-associated tumor, with an exceptionally low survival rate due to its challenging diagnostic approach. So far, its treatment is based on a combination of approaches (such as surgical resection with or rarely without chemotherapeutic agents), but with finite limits. Thus, looking for additional space to improve pancreatic tumorigenesis therapeutic approach, research has focused on gene therapy with unexpectedly growing horizons not only for the treatment of inoperable pancreatic disease, but also for its early stages. In vivo gene delivery viral vectors, despite few disadvantages (possible immunogenicity, toxicity, mutagenicity, or high cost), could be one of the most efficient cancer gene therapeutic strategies for clinical application due to their superiority compared with other systems (ex vivo delivery strategies). Their dominance consists of simple preparation, easy operation and a wide range of functions. Adenoviruses are one of the most common used vectors, inducing strong immune as well as inflammatory reactions. Oncolytic virotherapy, using the above mentioned in vivo viral vectors, is one of the most promising non-pathogenic, highly-selective cytotoxic anti-cancer therapy using anti-cancer agents with high anti-tumor potency and strong oncolytic effect. There have been a variety of targeted therapeutic and pre-clinical strategies tested for gene therapy in pancreatic cancer such as gene-editing systems (e.g., clustered regularly interspaced palindromic repeats-Cas9), RNA interference technology (e.g., microRNAs, short hairpin RNA or small interfering RNA), adoptive immunotherapy and vaccination (e.g., chimeric antigen receptor T-cell therapy) with encouraging results.

Keywords: Pancreatic cancer, Gene therapy, Viral vectors, Gene editing, miRNA, siRNA, Oncolytic virotherapy

Core Tip: Pancreatic cancer still remains one of the leading causes of cancer deaths worldwide. While there are various therapeutic approaches established, there is still a crucial need for improvement of conventional treatments and establishment of novel therapies to increase efficacy. This review exhibits an overview of the most promising present and future prospects regarding gene therapy which offers a new favorable opportunity not only to tackle with an inoperable pancreatic cancer, but also, to treat effectively its early stages.