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Antiangiogenic Drugs in Cancer Therapy: Effect on Advanced Renal Cell Carcinoma

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Molecular Mechanisms of Angiogenesis

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Abstract

After the first report demonstrating efficacy of an anti-angiogenic treatment in patients suffering from metastatic renal cell cancer in 2003, intense developments of VEGF monoclonal antibodies or tyrosine kinases inhibitors directed against VEGF receptors were done. This approach was successful and lead to the registration of anti angiogenic agents in at least 8 types of different cancers. Metastatic renal carcinoma, a chemo resistant tumor, appears to be very sensitive to these agents. Today several different agents, directly or undirectly aimed at the VEGF pathway, are available for treatment. Indeed, the clear cell renal carcinoma that represents more than 75% of cases, commonly achieved some inactivation of the Von Hippel Lindau (VHL) gene. As a consequence, the hypoxia inductive factor (HIF) accumulates in tumor cells, leading to the upregulation downstream genes, particularly VEGF and PDGF. In addition, renal cell carcinoma cells produce high amounts of VEGF and overexpressed different types of VEGF receptors. The specific carcinogenesis explains that anti-angiogenic agents have double targets in this tumor: the endothelial cells of the neo-vascularization as well as tumor cells.

In conclusion, the development of effective anti-angiogenic treatment for advanced renal cancer was responsible for a substantial impact on outcome for patients.

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Authors and Affiliations

  1. Centre Léon Bérard, Université Claude Bernard Lyon I, Lyon, France

    Sylvie Négrier

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  1. Sylvie Négrier
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Correspondence to Sylvie Négrier .

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Editors and Affiliations

  1. UMR 1036, Biologie du Cancer et de l’Infection, Institut de Recherches en Technologies et Sciences pour le Vivant, Université Grenoble-Alpes, Grenoble, France

    Jean-Jacques Feige

  2. Institute for Research on Cancer and aging of Nice (IRCAN), University of Nice Sophia Antipolis, Nice, France

    Gilles Pagès

  3. CNRS UMR8161, Institut Pasteur de Lille, Institut de Biologie de Lille, Lille, France

    Fabrice Soncin

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Négrier, S. (2014). Antiangiogenic Drugs in Cancer Therapy: Effect on Advanced Renal Cell Carcinoma. In: Feige, JJ., Pagès, G., Soncin, F. (eds) Molecular Mechanisms of Angiogenesis. Springer, Paris. https://doi.org/10.1007/978-2-8178-0466-8_18

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