Molecular mechanisms of metastatic peritoneal dissemination in gastric adenocarcinoma
Deanna Ng, David P. Cyr, Shawn Khan, Fahima Dossa, Carol J. Swallow, Karineh Kazazian
Abstract
Peritoneal dissemination portends a dismal prognosis in patients with gastric adenocarcinoma in the context of limited effective treatments. The underlying cellular processes that drive gastric peritoneal carcinomatosis remain unclear, limiting the application of novel targeted therapies. In this comprehensive review, we aimed to identify and summarize all existing context-dependent molecular mechanisms that have been implicated in peritoneal dissemination and peritoneal carcinomatosis establishment from primary gastric adenocarcinoma. We applied a multilevel examination including data from in vivo murine models using human gastric cancer cell lines, in vitro technique-based studies, ex vivo models, and genomic/proteomic and molecular profiling analyses to report on various aspects of gastric cancer peritoneal metastasis biology. Mechanisms promoting peritoneal dissemination were grouped into three main functional categories: (1) intrinsic cancer cell biology, (2) cancer cell-peritoneal surface adhesion, and (3) peritoneal tumor microenvironment. We identified significant overlap among the three categories, indicating a complex interplay between multiple molecular mechanisms. By interrupting these pathways, peritoneal-directed therapies have the potential to improve quality and length of life in patients with high-risk primary gastric cancer.