Controlling angiogenesis in gastric cancer: A systematic review of anti-angiogenic trials

Shan, Fei; Miao, Rulin; Xue, Kan; Li, Zhemin; Li, Ziyu; Bu, Zhaode; Wu, Aiwen; Zhang, Lianhai; Wu, Xiaojiang; Zong, Xiang-Long; Wang, Xiaohong; Li, Shuangxi; Ji, Xin; Jia, Ziyu; Li, Ziran; Ji, Jiafu

doi:10.1016/j.canlet.2015.12.023

Cited by 25 publications

(22 citation statements)

References 27 publications

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“…A systematic review on this topic by Shan et al [ 121 ] found a total number of 16 trials investigating tyrosine kinase inhibitors in the therapy of gastric cancer. Only apatinib and, to a certain extent, regorafenib, showed positive results while all other therapies failed to show any benefit compared to standard therapy.…”

Section: Clinical Trialsmentioning

confidence: 99%

Angiogenesis and Anti-Angiogenic Therapy in Gastric Cancer

Nienhüser

Schmidt

2017

IJMS

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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.

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Section: Clinical Trialsmentioning

confidence: 99%

Angiogenesis and Anti-Angiogenic Therapy in Gastric Cancer

Nienhüser

Schmidt

2017

IJMS

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“…Apatinib is a novel receptor tyrosine kinase inhibitor that targets VEGFR2 with a high specificity. It is an orally bioavailable agent that has shown a favorable anti-tumor efficacy with manageable side effects [10][11][12]. Based on the results of a multi-centered phase III clinical trial, it has been concluded that apatinib may significantly improve the survival of patients with advanced gastric cancers [13].…”

Section: Introductionmentioning

confidence: 99%

Apatinib inhibits glycolysis by suppressing the VEGFR2/AKT1/SOX5/GLUT4 signaling pathway in ovarian cancer cells

Chen

Cheng

et al. 2019

Cell Oncol.

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Background Apatinib is a tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2 (VEGFR2), and has shown encouraging therapeutic effects in various malignant tumors. As yet, however, the role of apatinib in ovarian cancer has remained unknown. Here, we sought to elucidate the role of apatinib in the in vitro and in vivo viability and proliferation of ovarian cancer cells, as well as in glucose metabolism in these cells. Methods The effects of apatinib on ovarian cancer cell viability and proliferation were assessed using Cell Counting Kit-8 (CCK-8) and colony formation assays, respectively. The expression of VEGFR2/AKT1/SOX5/GLUT4 pathway proteins was assessed using Western blotting, and glucose uptake and lactate production assays were used to detect glycolysis in ovarian cancer cells. SOX5 was exogenously over-expressed and silenced in ovarian cancer cells using expression vector and shRNA-based methods, respectively. RNA expression analyses were performed using RNA-seq and gene-chip-based methods. GLUT4 promoter activity was assessed using a dual-luciferase reporter assay. The expression of p-VEGFR2 (Tyr1175), p-AKT1 (Ser473), p-GSK3β (Ser9), SOX5 and GLUT4 in xenograft tissues was assessed using immunohistochemistry (IHC). Results We found that apatinib inhibited the in vitro and in vivo viability and proliferation in Hey and OVCA433 ovarian cancer cells in a dose-dependent and time-dependent manner. We also found that apatinib effectively suppressed glucose uptake and lactate production by blocking the expression of GLUT4 in these cells. In addition, we found that SOX5 predominantly rescued the inhibitory effect of apatinib on GLUT4 expression by activating its promoter. Finally, we found that apatinib regulated the expression of SOX5 by suppressing the VEGFR2/AKT1/GSK3β signaling pathway. Conclusions From our results, we conclude that apatinib suppresses the in vitro and in vivo viability and proliferation of ovarian cancer cells, as well as glycolysis by inhibiting the VEGFR2/AKT1/GSK3β/SOX5/GLUT4 signaling pathway. Apatinib may serve as a promising drug for the treatment of ovarian cancer.

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“…Unfortunately, in the randomized phase III Avastin in Gastric Cancer (AVAGAST) study, the combination of chemotherapy and bevacizumab did not show a beter overall survival extension in the irst-line treatment when compared to advanced GC patients, who only subjected chemotherapy [82]. Intriguingly, REGARD and RAINBOW trials using VEGFR2 targeting antibody ramucirumab have also shown a signiicant increase in the overall survival of patients with advanced GC [83]. It can be partially explained by the geographical diferences of GC patients.…”

Section: The Tumor Microenvironment and Gastric Carcinogenesismentioning

confidence: 99%

Molecular Pathogenesis of Gastric Adenocarcinoma

Kang¹,

Zhang²,

To³

2018

Stomach Disorders

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The incidence and mortality of gastric cancer (GC) rank top ive and top three, respectively, among cancers around the world. It is an intricate malignancy caused by the reciprocity of intrinsically genetic, environmental, and host-related elements. The silent property, advanced clinical characterization, and potential heterogeneity have made GC a thorny disease with a high death rate. The increasing knowledge of the abundant genetic abnormalities regarding GC will deinitely elongate the patients' survival. Scientists have been working hard to discover the myths beneath gastric tumorigenesis: novel biomarkers have been established, and cell transduction cascades have been well described. The study grouping GC into four molecular subtypes by The Cancer Genome Atlas (TCGA) broadens our horizon of GC etiologies. Knowledge regarding to the sophisticated networks in tumor microenvironment also bring new insights into the mechanisms assist GC development. In the future, people will strive for translating more research achievements into clinical utility. Successful translational medicine will lead to new methods for early GC diagnosis and precise medical strategies for individuals.

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Controlling angiogenesis in gastric cancer: A systematic review of anti-angiogenic trials

Cited by 25 publications

References 27 publications

Angiogenesis and Anti-Angiogenic Therapy in Gastric Cancer

Angiogenesis and Anti-Angiogenic Therapy in Gastric Cancer

Apatinib inhibits glycolysis by suppressing the VEGFR2/AKT1/SOX5/GLUT4 signaling pathway in ovarian cancer cells

Molecular Pathogenesis of Gastric Adenocarcinoma

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