Abstract

Simple SummaryThe aberrant expression of several micro RNAs (miRNAs) has been shown to be involved in neoplastic angiogenesis, which is a crucial mechanism in gastric cancer onset and progression. In this review, the possible prognostic and predictive roles of angiogenesis-related miRNAs as novel biomarkers of gastric cancer have been evaluated, but neither tissue nor circulating biomarkers have shown a predictive role for response to anti-angiogenic treatment. Nevertheless, we consider that in future studies, miRNAs should be evaluated as candidate biomarkers with prognostic and predictive features.Gastric cancer (GC) is the fifth most frequently diagnosed malignant tumor and the third highest cause of cancer mortality worldwide. For advanced GC, many novel drugs and combinations have been tested, but results are still disappointing, and the disease is incurable in the majority of cases. In this regard, it is critical to investigate the molecular mechanisms underlying GC development. Angiogenesis is one of the hallmarks of cancer with a fundamental role in GC growth and progression. Ramucirumab, a monoclonal antibody that binds to vascular endothelial growth factor-2 (VEGFR-2), is approved in the treatment of advanced and pretreated GC. However, no predictive biomarkers for ramucirumab have been identified so far. Micro RNAs (miRNAs) are a class of evolutionarily-conserved single-stranded non-coding RNAs that play an important role (via post-transcriptional regulation) in essentially all biologic processes, such as cell proliferation, differentiation, apoptosis, survival, invasion, and migration. In our review, we aimed to analyze the available data on the role of angiogenesis-related miRNAs in GC.

Highlights

  • We identified five groups: (1) Micro RNAs (miRNAs) related to the vascular endothelial growth factor (VEGF) pathway, (2) miRNAs involved in the hypoxia inducible factor (HIF) pathway, (3)

  • MiRNAs related to hepatocyte growth factor (HGF)/c-MET signaling, (4) miRNAs involved in the phosphatidylinositol 3-kinase (PI3K) pathway, and

  • We will briefly describe the importance in the angiogenesis process of these five pathways, and we will detail, for each of them, the significant studies about angiogenesis-related miRNAs that we have found through our literature search

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Summary

Introduction

Angiogenesis partakes in multiple aspects of tumor biology, including dissemination and metastasis processes [2], metabolic deregulation [3], and cancer stem cell maintenance [4,5]. Angiogenesis is a complex process by which new blood vessels are formed from pre-existing ones [6]. Within tumors, an “angiogenic switch” is always activated, leading to the continuous generation of new vessels [7]. This “angiogenic switch” is governed by the upregulation of pro-angiogenic and downregulation of anti-angiogenic signals produced by tumor cells or the tumor microenvironment [8,9,10]

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