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  • Review Article
  • Published:

Molecular targets on the horizon for kidney and urothelial cancer

Nature Reviews Clinical Oncology volume 10, pages 557–570 (2013)Cite this article

Subjects

Key Points

  • Whole-genome sequencing is helping to facilitate the discovery of biomarkers of drug sensitivity in both renal cell carcinoma (RCC) and urothelial tumours

  • Urothelial carcinomas contain mutations in multiple genes that are potentially druggable, although clinical data supporting the use of agents targeting these mutations in this disease is still in its infancy

  • Some data linking molecular alterations and clinical outcome is emerging in RCC; overall survival in RCC has improved and patients are being treated for increasingly longer periods of time

  • Genomic and epigenomic mining in RCC has uncovered novel genes and pathways involved in tumorigenesis, genomic regulation, tumour classification and mechanisms of resistance in the various forms of RCC

Abstract

As whole-genome sequencing technology rapidly advances, the insights gained from deciphering cancer genomes are shifting the paradigm in the diagnosis and treatment of cancer with the promise of individualized treatment for each patient. Information gained in this way is extensive for certain cancers, but fairly limited in renal cell carcinomas and urothelial carcinoma. Mutations in multiple, potentially druggable genes have been identified in urothelial carcinomas; however, the association between molecular alterations and clinical outcome has not yet been robustly demonstrated. Data in this area are emerging in renal cell carcinoma, leading to the development of targeted agents that have improved overall survival. Unfortunately, these treatments rarely yield complete responses, are not curative, and development of resistance ensues. This Review will focus on the biology of non-hormonally driven urological cancers. We discuss how approaches using whole-genome sequencing can facilitate the discovery of biomarkers of drug sensitivity in both renal cell carcinomas and urothelial carcinomas. For renal cell carcinomas, we will describe how genomic and epigenomic mining has uncovered novel genes and pathways involved in tumorigenesis, tumour classification and mechanisms of resistance in the various subsets of this disease and the potential for exploiting these discoveries in the clinic.

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Figure 1: Signalling pathways involved in cell growth, angiogenesis and metastasis in RCC.
Figure 2: Therapeutic targets in urothelial tumours.

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Authors and Affiliations

  1. Dana-Farber and Brigham and Women's Cancer Center, Harvard Medical School, 450 Brookline Avenue, Boston, 02215, MA, USA

    Joaquim Bellmunt

  2. Hospital del Mar-IMIM-IMAS, Doctor Aiguader 88, Barcelona, 08003, Spain

    Joaquim Bellmunt

  3. National Cancer Centre Singapore, National Cancer Centre, 11 Hospital Drive, Singapore, 169610, Singapore

    Bin T. Teh

  4. Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale Luduvico Antonio Scuro 10, Verona, 37134, Italy

    Giampaolo Tortora

  5. Non-Prostate Genitourinary Malignancies, Memorial Sloan-Kettering Cancer Center, Weill-Cornell Medical College, 1275 York Avenue, New York, 10065, NY, USA

    Jonathan E. Rosenberg

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All the authors researched data for the article, made a substantial contribution to the discussion of the content, wrote the article and reviewed and edited it prior to submission.

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Correspondence to Joaquim Bellmunt.

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Competing interests

J. Bellmunt is a consultant for Novartis, OncoGenex and Pfizer. J. E. Rosenberg is a consultant for Boehringer-Ingelheim, Bristol-Myers Squibb, Dendreon, and OncoGenex. B. Teh and G. Tortora declare no competing interests.

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Bellmunt, J., Teh, B., Tortora, G. et al. Molecular targets on the horizon for kidney and urothelial cancer. Nat Rev Clin Oncol 10, 557–570 (2013). https://doi.org/10.1038/nrclinonc.2013.155

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