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Resistance to Antiangiogenic Treatments via Upregulation of Substitution Pathways

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Book cover Molecular Mechanisms of Angiogenesis

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Abstract

The development of an abnormal vascular network is a key phenomenon in tumor progression. This finding has promoted the development of therapies targeting growth factors involved in the formation of pathological blood vessels (vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2). The overall purpose of this therapeutic approach is to asphyxiate tumors by oxygen and/or nutrient deprivation in the blood flow. Inhibitors of the major growth factors or of their receptors involved in tumor neovascularization named antiangiogenic therapies have been approved for the treatment of colon, breast, lung, kidney, brain, and ovarian cancers. Although some patients benefit greatly from treatments with long-term remissions, in most patients the remaining tumor cells acquire invasive properties and/or disseminate remotely from the primary tumor when surgery has not been underwent or in case of tumor regrowth despite initial size reduction or stabilization during the first months of treatment. Hence, tumor cells acquire specific properties as a consequence of the selected pressure exerted by therapeutic agents to promote treatment evasion. Instead of having a curative effect, these agents cause disease progression with worsened outcomes. Indeed, a major issue for cancer patients treated with antiangiogenic drugs is the recurrence of metastases and even the development of new metastatic niches. In this review, we will describe the different mechanisms associated with tumor recurrence as a consequence of the selected pressure exerted by antiangiogenic treatments.

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Authors and Affiliations

  1. Centre Scientifique de Monaco, Quai Antoine Ier, Monaco

    Renaud Grépin

  2. Institute for Research on Cancer and Aging of Nice (IRCAN) UMR CNRS 7284/ U INSERM 1081, University of Nice Sophia Antipolis, Nice, France

    Mélanie Guyot & Gilles Pagès

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  1. Renaud Grépin
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  2. Mélanie Guyot
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  3. Gilles Pagès
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Correspondence to Gilles Pagès .

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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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This work was supported by the National Institute of Cancer (INCA, Contract VEGFIL), the French Association for Cancer Research (ARC), the Fondation de France, the Conseil Général des Alpes Maritimes, and the “Association pour la Recherche sur les Tumeurs du Rein (ARTuR).”

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Grépin, R., Guyot, M., Pagès, G. (2014). Resistance to Antiangiogenic Treatments via Upregulation of Substitution Pathways. In: Feige, JJ., Pagès, G., Soncin, F. (eds) Molecular Mechanisms of Angiogenesis. Springer, Paris. https://doi.org/10.1007/978-2-8178-0466-8_20

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