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Therapies Targeting the Tumor Stroma and the VEGF/VEGFR Axis in Pancreatic Ductal Adenocarcinoma: a Systematic Review and Meta-Analysis

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Abstract

Abundant tumor stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and is suggested to play a role in the resistance of this deadly disease to systemic treatment. Despite promising results from preclinical studies, clinical trials with therapies targeting the tumor stroma and the vascular endothelial growth factor (VEGF) and its receptor VEGFR yielded conflicting results. With this systematic review and meta-analysis, we aim to summarize the existing evidence in this important field with a special focus on anti-VEGF/VEGFR therapy. A total of 24 clinical studies were included in the qualitative synthesis, and six randomized controlled trials (RCTs) investigating anti-VEGF/VEGFR agents were further included in the quantitative synthesis. The qualitative synthesis revealed a treatment advantage of combined therapy with nab-paclitaxel, while the meta-analysis on anti-VEGF/VEGFR drugs demonstrated marginal improvement of objective response rates and progression-free survival, but not overall survival. Stroma targeting is a promising and rapidly-developing treatment strategy in PDAC. However, novel drugs balancing stroma depletion and modulation are needed.

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Funding

The authors would like to acknowledge the following institutes for their financial support of the current study: National Natural Science Foundation of China (No. 81672449 to YM), the Innovation Capability Development Project of Jiangsu Province (No. BM2015004 to YM), Clinical Frontier Technology of Jiangsu Provincial Science and Technology Department (No. BE2016788 to KJ). The source of funding did not contribute to study design, data analysis, or manuscript writing and revision.

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  1. Zipeng Lu and Maximilian Weniger contributed equally to this work.

Authors and Affiliations

  1. Pancreas Center & Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Zipeng Lu, Kuirong Jiang, Kai Zhang & Yi Miao

  2. Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians-University, Marchioninistraße 15, 81377, Munich, Germany

    Zipeng Lu, Maximilian Weniger, Alexander Bazhin, Jens Werner & Jan G. D’Haese

  3. Department of Internal Medicine III and Comprehensive Cancer Center, Ludwig Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany

    Stefan Boeck

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  1. Zipeng Lu
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Correspondence to Yi Miao.

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Conflict of Interest

Stefan Boeck acted as a consultant, and received honoraria for scientific presentations and research funding from Celgene; Zipeng Lu, Maximilian Weniger, Kuirong Jiang, Kai Zhang, Alexander Bazhin, Yi Miao, Jens Werner, and Jan G. D’Haese declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Lu, Z., Weniger, M., Jiang, K. et al. Therapies Targeting the Tumor Stroma and the VEGF/VEGFR Axis in Pancreatic Ductal Adenocarcinoma: a Systematic Review and Meta-Analysis. Targ Oncol 13, 447–459 (2018). https://doi.org/10.1007/s11523-018-0578-x

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