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  • Review Article
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Targeted therapies in bladder cancer: an overview of in vivo research

Nature Reviews Urology volume 12, pages 681–694 (2015)Cite this article

Subjects

Key Points

  • Over the past 20 years, survival of patients with muscle-invasive bladder cancer has not improved

  • None of the targeted therapies that are approved for other cancers have been approved for the treatment of bladder cancer

  • The small number of clinical trials that have been performed in patients with bladder cancer had limited success owing to several limitations

  • Specific oncogenic mutations in different cell lines used in in vivo research might render these cell lines insensitive to the therapy that is being investigated

  • Inhibition of EGFR, FGFR-3, VEGF, mTOR, STAT3, the androgen receptor and CD24 resulted in inhibition of tumour growth in multiple in vivo studies

  • Careful patient selection in clinical trials based on the molecular profile of the tumour will be essential in demonstrating benefit of new targeted therapies

Abstract

Survival of patients with muscle-invasive bladder cancer is poor and new therapies are needed. Currently, none of the targeted agents that are approved for cancer therapy have been approved for the treatment of bladder cancer and the few clinical trials that have been performed had limited success, often owing to a lack of efficacy and toxic effects. However, many other novel targeted agents have been investigated in animal models of bladder cancer. EGFR, FGFR-3, VEGF, mTOR, STAT3, the androgen receptor and CD24 are molecular targets that could be efficiently inhibited, resulting in reduced tumour growth, and that have been investigated in multiple independent studies. Several other targets, for example COX-2, IL-12, Bcl-xL, livin and choline kinase α, have also been observed to inhibit tumour growth, but these findings have not been replicated to date. Limitations of several studies include the use of cell lines with mutations downstream of the target, providing resistance to the tested therapy. Furthermore, certain technologies, such as interfering RNAs, although effective in vitro, are not yet ready for clinical applications. Further preclinical research is needed to discover and evaluate other possible targets, but several validated targets are now available to be studied in clinical trials.

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Figure 1: Cellular processes involved in cancer development.
Figure 2: Cellular pathways affected in bladder cancer and targeting therapies.

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Acknowledgements

We would like to acknowledge W. M. Bramer for his contribution to the literature search and database management. This study was funded by an Erasmus MC 2012 grant.

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Authors and Affiliations

  1. Department of Pathology, Erasmus MC, PO Box 2040, Rotterdam, 3000, CA, Netherlands

    Kim E. M. van Kessel & Ellen C. Zwarthoff

  2. Department of Urology, Erasmus MC, PO Box 2040, Rotterdam, 3000, CA, Netherlands

    Tahlita C. M. Zuiverloon, Arnout R. Alberts & Joost L. Boormans

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  1. Kim E. M. van Kessel
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  2. Tahlita C. M. Zuiverloon
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Contributions

E.C.Z., K.E.M.v.K., T.C.M.Z. and A.R.A. researched data for the article. E.C.Z., K.E.M.v.K., T.C.M.Z. and J.L.B. substantially contributed to discussion of the content. E.C.Z., K.E.M.v.K. and J.L.B. wrote article. All authors contributed to review and editing of the manuscript before submission.

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Correspondence to Ellen C. Zwarthoff.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

In vivo studies using KU-7 animal models (PDF 90 kb)

Supplementary Table 2

In vivo studies investigating targeting of receptor tyrosine kinases and angiogenesis (PDF 110 kb)

Supplementary Table 3

In vivo studies investigating targeting of signal transduction pathways (PDF 114 kb)

Supplementary Table 4

In vivo studies investigating targeting of cell cycle, apoptosis, translation and metabolism (PDF 95 kb)

Supplementary Table 5

In vivo studies investigating targeting of metastasis, the immune system and other strategies (PDF 107 kb)

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van Kessel, K., Zuiverloon, T., Alberts, A. et al. Targeted therapies in bladder cancer: an overview of in vivo research. Nat Rev Urol 12, 681–694 (2015). https://doi.org/10.1038/nrurol.2015.231

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