Molecular mechanisms of peritoneal dissemination in gastric cancer

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: Biomarker; Gastric cancer; Microenvironment; Molecular target; Peritoneal dissemination.

Figure 1

Steps for formation of peritoneal dissemination in gastric cancer. CDH1: Cadherin 1, E-cadherin; ANXA1: Annexin 1; NRAGE: Neurotrophin receptor-interacting melanoma antigen-encoding gene homolog; HIF1A: Hypoxia-inducible factor-1α subunit; PTEN: Phosphatase and tensin homolog; CXCR4: C-X-C motif chemokine receptor 4; CXCL12: C-X-C motif chemokine ligand 12; EGFR: Epidermal growth factor receptor; AREG: Amphiregulin; HBEGF: Heparin-binding EGF-like growth factor; MMP7: Matrix metalloproteinase 7; CTGF: Connective tissue growth factor; MELK: Maternal embryonic leucine zipper kinase; VEGFA: Vascular endothelial growth factor A; IRX1: Iroquois homeobox 1.