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World J Gastrointest Oncol. Aug 15, 2018; 10(8): 202-210
Published online Aug 15, 2018. doi: 10.4251/wjgo.v10.i8.202
Shattering the castle walls: Anti-stromal therapy for pancreatic cancer
Ozkan Kanat, Hulya Ertas
Ozkan Kanat, Hulya Ertas, Department of Medical Oncology, Faculty of Medicine, Uludag University, Bursa 16059, Turkey
Author contributions: Kanat O assigned the topic, wrote the manuscript, and generated the figure; Ertas H contributed to the collection of the relevant references and writing manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Open-Access: 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/
Correspondence to: Ozkan Kanat, MD, PhD, Professor, Department of Medical Oncology, Faculty of Medicine, Uludag University, Gorukle, Bursa 16059, Turkey. ozkanat@uludag.edu.tr
Telephone: +90-224-2951321
Received: March 30, 2018
Peer-review started: March 30, 2018
First decision: April 23, 2018
Revised: June 19, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: August 15, 2018
Abstract

Despite the availability of potent chemotherapy regimens, such as 5-fluorouracil, folinic acid, irinotecan, and oxaliplatin (FOLFIRINOX) and nab-paclitaxel plus gemcitabine, treatment outcomes in metastatic pancreatic cancer (PC) remain unsatisfactory. The presence of an abundant fibrous stroma in PC is considered a crucial factor for its unfavorable condition. Apparently, stroma acts as a physical barrier to restrict intratumoral cytotoxic drug penetration and creates a hypoxic environment that reduces the efficacy of radiotherapy. In addition, stroma plays a vital supportive role in the development and progression of PC, which has prompted researchers to assess the potential benefits of agents targeting several cellular (e.g., stellate cells) and acellular (e.g., hyaluronan) elements of the stroma. This study aims to briefly review the primary structural properties of PC stroma and its interaction with cancer cells and summarize the current status of anti-stromal therapies in the management of metastatic PC.

Keywords: Pancreatic cancer, Stroma, Stellate cells, Hyaluronan, Secreted protein acidic and rich in cysteine

Core tip: The primary characteristic of pancreatic adenocarcinoma is the presence of an extensive desmoplastic stroma around neoplastic cells. In this study, we aim to briefly review the primary structural properties of pancreatic cancer (PC) stroma and its interaction with cancer cells and summarize the current status of anti-stromal therapies in the management of metastatic PC.