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Angiogenic inhibitors: a new therapeutic strategy in oncology

Nature Clinical Practice Oncology volume 2, pages 562–577 (2005)Cite this article

Abstract

Angiogenesis is a multistep, complex and tightly regulated process that is necessary for tumor growth and metastasis. Based on data of preclinical models, several antiangiogenic compounds has been shown to modify activated tumor endothelium, which suggests that these compounds can improve cytotoxic drug delivery. Such agents have entered clinical trials as single agents or in combination with cytotoxic drugs, and have shown promising antitumor activity. The pharmacodynamic and pharmacokinetic characteristics of antiangiogenic drugs are reviewed here. Most of the early clinical testing of these agents was conducted in patients with advanced disease resistant to standard therapies. Phase III trials compared the efficacy of standard chemotherapy alone with standard chemotherapy in combination with an experimental angiogenesis inhibitor. Although some of these studies were negative or controversial, recent studies validated in large clinical trials with an anti-vascular endothelial growth factor antibody demonstrated significant clinical benefit and renewed enthusiasm for this therapeutic strategy. This review describes the clinical studies of antiangiogenic agents and highlights the challenges related to choosing appropriate strategies for the selection of patients, study design and choice of appropriate endpoints for the studies' development.

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Figure 1: Regulation and function of vascular endothelial growth factor.
Figure 2: Mechanisms of tumor angiogenesis.
Figure 3: Classification of angiogenesis inhibitors.

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Acknowledgements

Studies supported in part by the Associazione Italiano per le Terapie Biologiche Innovative (AITBI), Italy.

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Authors and Affiliations

  1. G Gasparini is the Director of and R Longo is Junior Assistant at the Division of Medical Oncology, “San Filippo Neri” Hospital, Rome, Italy

    Giampietro Gasparini & Raffaele Longo

  2. Director of the Department of Clinical Trials and Research at the Tokyo Metropolitan Cancer and Infectious Disease Centre Komagome Hospital, Tokyo, Japan

    Masakazu Toi

  3. Genentech Fellow in the Department of Molecular Oncology at Genentech, Inc., San Francisco, CA, USA

    Napoleone Ferrara

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  1. Giampietro Gasparini
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Correspondence to Giampietro Gasparini.

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Competing interests

Napoleone Ferrara is an employer and shareholder of Genentech Inc, which manufactures bevacizumab.

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Gasparini, G., Longo, R., Toi, M. et al. Angiogenic inhibitors: a new therapeutic strategy in oncology. Nat Rev Clin Oncol 2, 562–577 (2005). https://doi.org/10.1038/ncponc0342

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