Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2016; 22(30): 6829-6840
Published online Aug 14, 2016. doi: 10.3748/wjg.v22.i30.6829
Molecular mechanisms of peritoneal dissemination in gastric cancer
Mitsuro Kanda, Yasuhiro Kodera
Mitsuro Kanda, Yasuhiro Kodera, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Author contributions: Kanda M wrote the manuscript; Kodera Y revised the text and contributed to the scientific analysis in the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
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: Mitsuro Kanda, MD, PhD, Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. m-kanda@med.nagoya-u.ac.jp
Telephone: +81-52-7442249 Fax: +81-52-7442255
Received: March 26, 2016
Peer-review started: March 27, 2016
First decision: May 27, 2016
Revised: May 31, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: August 14, 2016
Abstract

Peritoneal dissemination represents a devastating form of gastric cancer (GC) progression with a dismal prognosis. There is no effective therapy for this condition. The 5-year survival rate of patients with peritoneal dissemination is 2%, even including patients with only microscopic free cancer cells without macroscopic peritoneal nodules. The mechanism of peritoneal dissemination of GC involves several steps: detachment of cancer cells from the primary tumor, survival in the free abdominal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space and proliferation with angiogenesis. These steps are not mutually exclusive, and combinations of different molecular mechanisms can occur in each process of peritoneal dissemination. A comprehensive understanding of the molecular events involved in peritoneal dissemination is important and should be systematically pursued. It is crucial to identify novel strategies for the prevention of this condition and for identification of markers of prognosis and the development of molecular-targeted therapies. In this review, we provide an overview of recently published articles addressing the molecular mechanisms of peritoneal dissemination of GC to provide an update on what is currently known in this field and to propose novel promising candidates for use in diagnosis and as therapeutic targets.

Keywords: Gastric cancer, Peritoneal dissemination, Microenvironment, Biomarker, Molecular target

Core tip: Peritoneal metastasis is the most common form of recurrence in gastric cancer, and it is associated with a poor prognosis. The development of peritoneal metastasis is a multistep process, beginning with the detachment of cancer cells from the primary tumor, followed by their attachment to peritoneal mesothelial cells, retraction of the mesothelial cells, exposure of the basement membrane, proliferation and finally growth with induction of angiogenesis. The aim of this review is to provide an update of our knowledge of the molecular mechanisms that promote peritoneal dissemination in gastric cancer. This information may aid in the design of new and effective treatments and diagnostics for this condition.