Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG, Karamouzis MV. Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol 2020; 12(2): 173-181 [PMID: 32104548 DOI: 10.4251/wjgo.v12.i2.173]
Corresponding Author of This Article
Michalis V Karamouzis, MD, PhD, Associate Professor, Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, Athens 11527, Greece. mkaramouz@med.uoa.gr
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastrointest Oncol. Feb 15, 2020; 12(2): 173-181 Published online Feb 15, 2020. doi: 10.4251/wjgo.v12.i2.173
Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy
Panagiotis Sarantis, Evangelos Koustas, Adriana Papadimitropoulou, Athanasios G Papavassiliou, Michalis V Karamouzis
Panagiotis Sarantis, Evangelos Koustas, Athanasios G Papavassiliou, Michalis V Karamouzis, Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
Adriana Papadimitropoulou, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece
Michalis V Karamouzis, First Department of Internal Medicine, “Laiko” General Hospital, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
Author contributions: Sarantis P, Koustas E and Papadimitropoulou A have equal contribution; Sarantis P, Koustas E and Papadimitropoulou A made substantial contributions to acquisition, analysis and interpretation of data; Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG and Karamouzis MV made substantial contributions in the conception, design and interpretation of the data; Papavassiliou AG and Karamouzis MV made substantial contributions in drafting the manuscript and revising it critically for important intellectual content.
Conflict-of-interest statement: No potential conflicts of interest.
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: Michalis V Karamouzis, MD, PhD, Associate Professor, Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75, M. Asias Street, Athens 11527, Greece. mkaramouz@med.uoa.gr
Received: March 29, 2019 Peer-review started: April 3, 2019 First decision: November 11, 2019 Revised: November 28, 2019 Accepted: December 13, 2019 Article in press: December 13, 2019 Published online: February 15, 2020 Processing time: 323 Days and 23 Hours
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with an average 5-year survival rate of less than 10%. Unfortunately, the majority of patients have unresectable, locally advanced, or metastatic disease at the time of diagnosis. Moreover, traditional treatments such as chemotherapy, surgery, and radiation have not been shown to significantly improve survival. Recently, there has been a swift increase in cancer treatments that incorporate immunotherapy-based strategies to target all the stepwise events required for tumor initiation and progression. The results in melanoma, non-small-cell lung cancer and renal cell carcinoma are very encouraging. Unfortunately, the application of checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, in pancreatic cancer has been disappointing. Many studies have revealed that the PDAC microenvironment supports tumor growth, promotes metastasis and consists of a physical barrier to drug delivery. Combination therapies hold great promise for enhancing immune responses to achieve a better therapeutic effect. In this review, we provide an outline of why pancreatic cancer is so lethal and of the treatment hurdles that exist. Particular emphasis is given to the role of the tumor microenvironment, and some of the latest and most promising studies on immunotherapy in PDAC are also presented.
Core tip: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Treatments such as surgery, radiation, and chemotherapy have limited efficacy due to the extensive heterogeneity of genetic mutations and the dense stromal environment, among other causes. In recent years, immunotherapy has been successfully applied in the treatment of various types of cancers, and immunotherapy combined with the above treatments could create more favorable conditions for the fight against PDAC.
