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Targeting GRPR in urological cancers—from basic research to clinical application

Nature Reviews Urology volume 10, pages 235–244 (2013)Cite this article

Subjects

Abstract

Gastrin releasing peptide (GRP) is a regulatory peptide that acts through its receptor (GRPR) to regulate physiological functions in various organs. GRPR is overexpressed in neoplastic cells of most prostate cancers and some renal cell cancers and in the tumoral vessels of urinary tract cancers. Thus, targeting these tumours with specifically designed GRP analogues has potential clinical application. Potent and specific radioactive, cytotoxic or nonradioactive GRP analogues have been designed and tested in various animal tumour models with the aim of receptor targeting for tumour diagnosis or therapy. All three categories of compound were found suitable for tumour targeting in animal models. The cytotoxic and nonradioactive GRP analogues have not yet shown convincing tumour-reducing effects in human trials; however, the first clinical studies of radioactive GRP analogues—both agonists and antagonists—suggest promising opportunities for both diagnostic tumour imaging and radiotherapy of prostate and other GRPR-expressing cancers.

Key Points

  • Gastrin-releasing peptide (GRP) regulates physiological functions in various organs and has growth-stimulating properties in tumours

  • The GRP receptor (GRPR) is overexpressed in the neoplastic cells of most prostate cancers and in some renal cell cancers and in the tumoral vessels of urinary tract cancers

  • Potent and specific radioactive, cytotoxic or nonradioactive GRP analogues were found to be suitable targeting agents for diagnosis or therapy in animal models

  • Cytotoxic and nonradioactive GRP analogues have not yet shown convincing tumour-reducing effects in human trials

  • The first clinical study of radioactive GRP analogues suggests promising opportunities for the diagnosis and therapy of prostate and other cancers

  • Newly designed radiolabelled GRPR antagonists demonstrate better in vivo tumour uptake than radiolabelled GRPR agonists

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Figure 1: GRPR expression in prostate cancer.
Figure 2: GRPR expression in urinary bladder cancer.
Figure 3: Targeting cancer with nonradioactive GRPR antagonists.
Figure 4: Targeted radiotherapy with radiolabelled bombesin analogues.
Figure 5: Development of a bombesin-related radioligand.
Figure 6: Targeted cytotoxic therapy with a cytotoxic bombesin agonist.

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Acknowledgements

The authors thank Myreille Kuonen, Berne, for her excellent secretarial assistance.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Freiburg, Hugstetter Strasse 55, Freiburg, 79106, Germany

    Rosalba Mansi & Helmut R. Mäcke

  2. Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, P. O. Box 62, Murtenstrasse 31, Berne, CH-3010, Switzerland

    Achim Fleischmann & Jean C. Reubi

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  2. Achim Fleischmann
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  3. Helmut R. Mäcke
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  4. Jean C. Reubi
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Contributions

R. Mansi, H. R. Mäcke and J. C. Reubi researched data for the article. A. Fleischmann, H. R. Mäcke and J. C. Reubi made substantial contribution to discussion of content. R. Mansi and J. C. Reubi wrote the article. H. R. Mäcke and J. C. Reubi reviewed the manuscript before submission.

Corresponding author

Correspondence to Jean C. Reubi.

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Competing interests

R. Mansi, H. R. Mäcke and J. C. Reubi have received grant/research support (inc. clinical trials) from and are patent holders/applicants for Bayer. A. Fleischmann declares no competing interests.

Supplementary information

Supplementary Table 1

Amino acid sequences of bombesin-like peptides and their analogues (DOC 44 kb)

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Mansi, R., Fleischmann, A., Mäcke, H. et al. Targeting GRPR in urological cancers—from basic research to clinical application. Nat Rev Urol 10, 235–244 (2013). https://doi.org/10.1038/nrurol.2013.42

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