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Relevance of angiogenesis in neuroendocrine tumors

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Abstract

While traditional cytotoxic drugs have shown limited efficacy in neuroendocrine tumors (NETs), their biological features have been characterized and can be exploited therapeutically. Their most prominent trait is an extraordinary vascularization in low-grade NETs and an hypoxia-dependent angiogenesis in high-grade NETs, which is associated to a significant expression of many proangiogenic molecules. Therefore, several antiangiogenic compounds have been tested in these malignancies, and among these, sunitinib has demonstrated activity in pancreatic NET patients by dually targeting the VEGFR and PDGFR pathways. In spite of these efficacious clinical results, apparent resistance to antiangiogenic therapies has been described in NET animal models and in clinical trials. Therefore, overcoming antiangiogenic resistance is a crucial step in the subsequent development of antiangiogenic therapies. Several strategies have been postulated to fight resistance, but preclinical studies and clinical trials will investigate and address these therapeutic approaches in the coming years in order to overcome resistance to antiangiogenic therapies in NETs.

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Acknowledgments

The authors would like to thank Dr. Ramon Salazar for critical reading of the manuscript and helpful suggestions. The authors' work is supported by research grants from MICINN (SAF2009-08375, RTICC-RD2006-0092) and AGAUR (SGR681) from Spain.

Conflict of interest

The authors declare that no conflict of interest exists.

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Authors and Affiliations

  1. Hereditary Cancer Program, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain

    Alexandre Teulé

  2. Tumor Angiogenesis Group, Catalan Institute of Oncology—IDIBELL, Av. Gran Via, 199-203. E-08908 L’Hospitalet de Llobregat, Barcelona, Spain

    Oriol Casanovas

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  1. Alexandre Teulé
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Correspondence to Oriol Casanovas.

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Teulé, A., Casanovas, O. Relevance of angiogenesis in neuroendocrine tumors. Targ Oncol 7, 93–98 (2012). https://doi.org/10.1007/s11523-012-0217-x

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