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Oncogenes and angiogenesis: a way to personalize anti-angiogenic therapy?

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Abstract

The acquisition of oncogenic mutations and promotion of angiogenesis are key hallmarks of cancer. These features are often thought of as separate events in tumor progression and the two fields of research have frequently been considered as independent. However, as we highlight in this review, activated oncogenes and deregulated angiogenesis are tightly associated, as mutations in cancer cells can lead to perturbation of the pro- and anti-angiogenic balance thereby causing aberrant angiogenesis. We propose that normalization of the vascular network by targeting oncogenes in the tumor cells might lead to more efficient and sustained therapeutic effects compared to therapies targeting tumor vessels. We discuss how pharmacological inhibition of oncogenes in tumor cells restores a functional vasculature by bystander anti-angiogenic effect. As genetic alterations are tumor-specific, targeted therapy, which potentially blocks the angiogenic program activated by individual oncogenes may lead to personalized anti-angiogenic therapy.

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Acknowledgments

A warm thanks to Prof. Nancy E. Hynes, Dr. Jason W. Gill, and Dr. Alessio Noghero for critical reading and suggestions. The research leading to these results has received funding from the European Community’s Seventh Framework Programme under Grant agreement no. 259015 COLTHERES; AIRC 2010 Special Program Molecular Clinical Oncology 5xMille, Project no. 9970; Intramural Grant—5xmille 2008 Fondazione Piemontese per la Ricerca sul Cancro—ONLUS, AIRC IG Grant no. 12812. A. Bottos was supported by the Swiss Science Foundation (#310030_138417).

Conflict of interest

A. Bardelli owns stock in, and has received consultancy fees, from Horizon Discovery.

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  1. Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, PO Box 2543, 4058, Basel, Switzerland

    Alessia Bottos

  2. Department of Oncological Sciences, University of Torino, Strada prov 142, km 3.95, 10060, Candiolo, Turin, Italy

    Alberto Bardelli

  3. Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, Strada prov 142, km 3.95, 10060, Candiolo, Turin, Italy

    Alberto Bardelli

  4. Fondazione Italiana per la Ricerca sul Cancro Institute of Molecular Oncology, 20139, Milan, Italy

    Alberto Bardelli

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  1. Alessia Bottos
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Bottos, A., Bardelli, A. Oncogenes and angiogenesis: a way to personalize anti-angiogenic therapy?. Cell. Mol. Life Sci. 70, 4131–4140 (2013). https://doi.org/10.1007/s00018-013-1331-3

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  • DOI: https://doi.org/10.1007/s00018-013-1331-3

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