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Anti-Angiogenics in Pancreatic Cancer Therapy

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Tumor Angiogenesis

Abstract

Pancreatic cancer is a highly lethal disease. Up to date, the only curative approach is surgical resection, which is only possible in a limited number of patients by the time of diagnosis. Thus, the development of new therapeutic options besides chemotherapy is extremely important for patients who do not qualify for surgery due to local irresectability or systemic tumor spread. During development and progression of pancreatic tumors, angiogenesis is an important mechanism to supply blood, oxygen, and nutrients for the growing tumor mass. Several angiogenic factors play a critical role during this process, including vascular endothelial growth factor (VEGF), as well as multiple factors involved in tyrosine kinase pathways, all of which are potential targets for systemic treatment approaches.

Pancreatic ductal adenocarcinoma represents the biggest proportion among all pancreatic tumor entities. It is histopathologically characterized by a hypovascular appearance and pronounced peritumoral desmoplastic tissue as well as extracellular matrix. In numerous experimental and clinical studies, antiangiogenic therapy has been evaluated for pancreatic ductal adenocarcinoma with early promising results. However, in clinical phase III studies, only limited effects were achieved with targeted antiangiogenic approaches.

In contrast, pancreatic neuroendocrine tumors, which are typically hypervascularized, are much more sensitive to antiangiogenic substances. After a successful phase III study, sunitinib – a multi-targeted kinase inhibitor – has been approved for the treatment of this entity and is incorporated in current international guidelines as a second-line therapy recommendation.

The pathogenesis, diagnostic measures, as well as current experimental and clinical studies regarding angiogenesis and antiangiogenic therapy of both pancreatic ductal adenocarcinoma and neuroendocrine tumors are summarized described in this chapter.

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  1. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Thilo Hackert, Laura Wüsten & Markus W. Büchler

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  1. Thilo Hackert
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  2. Laura Wüsten
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  1. Tumor Biology Center, Freiburg, Baden-Württemberg, Germany

    Dieter Marmé

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Hackert, T., Wüsten, L., Büchler, M.W. (2017). Anti-Angiogenics in Pancreatic Cancer Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-31215-6_18-1

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