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Molecular mechanisms and clinical applications of angiogenesis

Abstract

Blood vessels deliver oxygen and nutrients to every part of the body, but also nourish diseases such as cancer. Over the past decade, our understanding of the molecular mechanisms of angiogenesis (blood vessel growth) has increased at an explosive rate and has led to the approval of anti-angiogenic drugs for cancer and eye diseases. So far, hundreds of thousands of patients have benefited from blockers of the angiogenic protein vascular endothelial growth factor, but limited efficacy and resistance remain outstanding problems. Recent preclinical and clinical studies have shown new molecular targets and principles, which may provide avenues for improving the therapeutic benefit from anti-angiogenic strategies.

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Figure 1: Modes of vessel formation.
Figure 2: Molecular basis of vessel branching.
Figure 3: Potential mechanisms of resistance to targeted VEGF therapy in cancer.

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Acknowledgements

We would like to acknowledge the late J. Folkman for inspiring us and others to work in the area of tumour angiogenesis. We would like to thank L. Claeson-Welch, H. Augustin, E. Dejana, S. Kozin, D. G. Duda, S. Goel, L. L. Munn, G. Sledge, R. Stupp and H. D. Suit for their comments, and L. Notebaert for help with the illustrations. We apologize to the authors whose work we could not cite because of the limit on the number of references. The work of P.C. is supported by a Federal Government Belgium grant (IUAP06/30), long-term structural Methusalem funding by the Flemish Government, a Concerted Research Activities Belgium grant (GOA2006/11), Leducq Transatlantic Network ARTEMIS and a grant from Flanders Research Foundation (FWO G.0673.08). The research of R.K.J. is supported by US National Institutes of Health grants P01-CA80124, R01-CA85140, R01-CA115767 and R01-CA126642, Federal Share/NCI Proton Beam Program Income, the National Foundation for Cancer Research and a Department of Defense Breast Cancer Research Innovator Award (W81XWH-10-1-0016).

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Correspondence to Peter Carmeliet or Rakesh K. Jain.

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R.K.J. reports receiving consulting fees from Astellas, AstraZeneca, Dyax, Enlight Biosciences, Genzyme, Millenium, MorphoSys, Noxxon and SynDevRx; lecture fees from Alnylam, Genzyme, Pfizer and MPM Capital; and grant support from Dyax, AstraZeneca, MedImmune and Roche; and owns equity in Enlight Biosciences and SynDevRx. P.C. reports receiving recent consulting fees from Roche, ThromboGenics and Astellas; lecture fees from Roche and Novartis; and grant support from ThromboGenics; and owns equity in ThromboGenics.

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Carmeliet, P., Jain, R. Molecular mechanisms and clinical applications of angiogenesis. Nature 473, 298–307 (2011). https://doi.org/10.1038/nature10144

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