Evidence Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2021; 27(17): 1847-1863
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1847
Pancreatic adenocarcinoma: Beyond first line, where are we?
Sara Cherri, Silvia Noventa, Alberto Zaniboni
Sara Cherri, Silvia Noventa, Alberto Zaniboni, Department of Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
Author contributions: Cherri S contributed drafting of the manuscript; Noventa S contributed tables and figures; Noventa S and Zaniboni A contributed critical revision of the manuscript for important intellectual content; all the authors read and approved the final manuscript.
Conflict-of-interest statement: Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (e.g., consultancies, stock ownership, equity interest, patent/Licensing arrangements) that might pose a conflict of interest in connection with the submitted 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: Sara Cherri, MD, Medical Assistant, Department of Oncology, Fondazione Poliambulanza, Via Bissolati 57, Brescia 25124, Italy. sara.m.cherri@gmail.com
Received: January 26, 2021
Peer-review started: January 26, 2021
First decision: February 27, 2021
Revised: March 9, 2021
Accepted: April 13, 2021
Article in press: April 13, 2021
Published online: May 7, 2021

Pancreatic cancer is considered one of the most aggressive cancers, with an increasing incidence in recent years. To date, chemotherapy is still the standard of care for advanced metastatic disease, unfortunately providing only a slight advantage in terms of survival. The molecular and cellular characteristics of pancreatic cancer cells, as well as the cells that characterize the pancreatic tumour microenvironment, are the basis of the mechanisms of resistance to treatment. After progression during first-line treatment, few patients are eligible for second-line treatment due to the loss of performance status. To date, a clear survival advantage has not yet been demonstrated for second-line chemotherapy. Precision medicine could be the key to increasing responses to cancer treatment and finally impacting survival in this difficult-to-treat disease. In this review, we analyze current recommendations in the second-line setting and potential future prospects.

Keywords: Pancreatic adenocarcinoma, Second-line, Chemotherapy, Targeted therapy, Immunotherapy

Core Tip: The incidence of pancreatic ductal adenocarcinoma is increasing, with anticipation of a large impact on the population. Despite achieving a survival gain in first-line treatment in the last decade, to date, little has been achieved in second-line treatment. The molecular and genetic characteristics of this tumour represent a fundamental challenge for preclinical and clinical research. In this review, we illustrate current clinical practice in second-line treatment for advanced pancreatic adenocarcinoma and the research landscape of potential future prospects.