Angiogenesis and Anti-Angiogenic Therapy in Gastric Cancer.

Henrik Nienhüser,Thomas Schmidt

doi:10.3390/ijms19010043

Henrik Nienhüser, Thomas Schmidt

Open Access

https://doi.org/10.3390/ijms19010043

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Abstract

Gastric cancer is one of the most frequent malignancies worldwide. Despite improvements in diagnosis and therapy, the overall prognosis remains poor. In the last decade, several anti-angiogenic drugs for cancer treatment have been approved and lately also introduced to gastric cancer treatment. While the initial trials focused only on unresectable or metastatic cancer, anti-angiogenic treatment is now also investigated in the perioperative and neoadjuvant setting. In this review, an overview of the role of angiogenesis and angiogenic factors in gastric cancer as well as anti-angiogenic treatment of gastric cancer is provided. Findings from in vitro and animal studies are summarized and put in a context with translational data on angiogenesis in gastric cancer. The most important angiogenic factors and their effect in gastric cancer are highlighted and clinical trials including anti-angiogenic drugs are discussed. Finally, an outlook of biomarkers for predicting response to anti-angiogenic treatment is presented, the ongoing trials on this topic are discussed and current challenges of anti-angiogenic therapy are outlined.

Highlights

Gastric cancer is killing more than one million people worldwide every year [1]
The purpose of this review is to focus on the current data of anti-angiogenic treatment in gastric cancer
We will provide an overview of different angiogenic cytokines and their role in tumor angiogenesis as well as on clinical trials investigating the effect of anti-angiogenic treatment

Summary

Introduction

Gastric cancer is killing more than one million people worldwide every year [1]. Even if diagnosis and perioperative therapy have improved over the last decades, outcome is still poor with overall 5-year survival rates of less than 40% [2,3,4,5]. Because of low response rates and the development of chemoresistance to the established chemotherapeutic regimens, anti-angiogenic drugs have gained more and more interest in the therapy of gastric cancer [6,7,8]. ECs can sense angiogenic signals and can respond to angiogenic signals by retaining a high plasticity. This is of most importance in pathological conditions such as wound healing and inflammation, in many disease conditions angiogenesis becomes deregulated and further supports the disease development instead of limiting it [10]. We will provide an overview of different angiogenic cytokines and their role in tumor angiogenesis as well as on clinical trials investigating the effect of anti-angiogenic treatment. We will give an outlook on the prediction of potential biomarkers and their help for an early diagnosis of the disease

Angiogenic Signaling and Pathways

Experimental In Vivo Data

Translational Data and Angiogenic Factors as Biomarkers

Clinical Trials

Findings

Challenges