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  • Review Article
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Targeting angiogenesis in oncology, ophthalmology and beyond

Nature Reviews Drug Discovery volume 22, pages 476–495 (2023)Cite this article

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Abstract

Angiogenesis is an essential process in normal development and in adult physiology, but can be disrupted in numerous diseases. The concept of targeting angiogenesis for treating diseases was proposed more than 50 years ago, and the first two drugs targeting vascular endothelial growth factor (VEGF), bevacizumab and pegaptanib, were approved in 2004 for the treatment of cancer and neovascular ophthalmic diseases, respectively. Since then, nearly 20 years of clinical experience with anti-angiogenic drugs (AADs) have demonstrated the importance of this therapeutic modality for these disorders. However, there is a need to improve clinical outcomes by enhancing therapeutic efficacy, overcoming drug resistance, defining surrogate markers, combining with other drugs and developing the next generation of therapeutics. In this Review, we examine emerging new targets, the development of new drugs and challenging issues such as the mode of action of AADs and elucidating mechanisms underlying clinical benefits; we also discuss possible future directions of the field.

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Fig. 1: Key milestones in angiogenesis research and drug discovery.
Fig. 2: Clinically approved anti-VEGF drugs for treating cancer and ophthalmic diseases.
Fig. 3: Angiogenic signalling molecules and their vascular functions.
Fig. 4: Anti-angiogenic drugs target different VEGF signalling events.
Fig. 5: Immunosuppressive functions of the tumour vasculature and VEGF.
Fig. 6: Targeting angiogenesis for treatment of ophthalmic diseases.

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Acknowledgements

The Cao laboratory is supported through research grants from the Swedish Research Council, the Hong Kong Centre for Cerebro-cardiovascular Health Engineering, the Swedish Cancer Foundation, the Swedish Children’s Cancer Foundation, the Strategic Research Areas (SFO) — Stem Cell and Regenerative Medicine Foundation, the Karolinska Institute Foundation, the Karolinska Institute distinguished professor award and the NOVO Nordisk Foundation. N.F. is supported by the National Institutes of Health (NIH), the Champalimaud Foundation, the L. Hillblom Foundation, the J. Pritzker family fund and start-up funds from the University of California, San Diego (UCSD). R.L. is supported by the NIH, the Novo Nordisk Foundation, the Roche Foundation, the Juvenile Diabetes Foundation, the Helmsley Foundation and the Gates Foundation.

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Authors and Affiliations

  1. Department of Microbiology, Tumour and Cell Biology, Karolinska Institute, Stockholm, Sweden

    Yihai Cao

  2. David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Robert Langer

  3. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Robert Langer

  4. Department of Pathology, University of California San Diego, La Jolla, CA, USA

    Napoleone Ferrara

  5. Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA

    Napoleone Ferrara

  6. Moores Cancer Center, University of California San Diego, La Jolla, CA, USA

    Napoleone Ferrara

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  1. Yihai Cao
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Y.C. and N.F. wrote the article. R.L. provided critical input on the content of the article.

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Cao, Y., Langer, R. & Ferrara, N. Targeting angiogenesis in oncology, ophthalmology and beyond. Nat Rev Drug Discov 22, 476–495 (2023). https://doi.org/10.1038/s41573-023-00671-z

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