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TGF-β in Human Disease pp 435–458Cite as

Targeting Pro-Angiogenic TGF-β Signaling in the Tumor Microenvironment

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Abstract

The recently developed targeted anti-angiogenic agents have been introduced into clinical practice over the course of the past decade. High hopes were placed on targeting the VEGF signaling pathway in endothelial cells following the preceding successful drug development in the preclinical setting. Indeed, the therapeutic efficacy observed in mouse models of cancer has in some cases been translated into clinical benefit for patients. Nevertheless, many anti-angiogenic therapies have failed to provide substantial improvement in survival in large phase III clinical trials. In the search for attractive and complementary angiogenic signaling pathways, the TGF-β family stands out as one of the most interesting. Our expanding knowledge on TGF-β signaling in the tumor vasculature has led to the development of specific inhibitors targeting TGF-β, ALK1, and endoglin. Many clinical trials exploring the concept of targeting pro-angiogenic TGF-β signaling are currently underway, and preliminary reports are encouraging. Here, we will discuss opportunities and challenges of targeting the TGF-β system for anti-angiogenic therapy of cancer.

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Abbreviations

ALK:

Activin receptor-like kinase

BMP:

Bone morphogenetic proteins

EC:

Endothelial cell

HHT:

Hereditary hemorrhagic telangiectasia

TGF-β:

Transforming growth factor-β

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

    Kristian Pietras & Sara I. Cunha

  2. Department of Laboratory Medicine Malmö, Lund University Cancer Center, Lund University, Lund, Sweden

    Kristian Pietras

Authors
  1. Kristian Pietras
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  2. Sara I. Cunha
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Correspondence to Kristian Pietras .

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Editors and Affiliations

  1. , Dept Medical Biochem Microbiol, Uppsala University, Box 582, Uppsala, SE-751 23, Sweden

    Aristidis Moustakas

  2. , Interdiscip. Grad. Sch. Med. Eng., University of Yamanashi, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan

    Keiji Miyazawa

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Pietras, K., Cunha, S.I. (2013). Targeting Pro-Angiogenic TGF-β Signaling in the Tumor Microenvironment. In: Moustakas, A., Miyazawa, K. (eds) TGF-β in Human Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54409-8_19

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