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Potential biofluid markers and treatment targets for renal cell carcinoma

Nature Reviews Urology volume 10, pages 336–344 (2013)Cite this article

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Abstract

Renal cell carcinoma (RCC) is the 13th most common cancer in the world and one of the few cancers for which incidence is increasing. This disease is generally asymptomatic at an early stage and is highly metastatic. Frequently discovered by physicians in the process of working up other diseases such as acute kidney injury, RCC is often discovered in an advanced form and many patients have metastases at the time of diagnosis. Given that life expectancy with currently approved therapies for metastatic RCC is approximately 1–2 years, biomarkers for RCC that will enable early detection are urgently needed. Although it is unlikely that highly sensitive and specific biomarkers will be identified in the near future that are useful for screening the general population, a noninvasive marker or set of markers could soon be used in general medicine, nephrology, and urology clinics to screen patients at increased risk of RCC. In addition to the ongoing need for RCC biomarkers, the frequent resistance reported with currently available targeted therapies makes the identification of new therapeutic targets similarly important. Many promising leads for new targeted therapies have come to light; some of these therapies are in clinical trials and others are still being evaluated in the laboratory.

Key Points

  • Renal cell carcinoma (RCC) incidence and mortality rates are increasing with every year; this disease is frequently asymptomatic in its early stages and can be highly metastatic

  • Seven targeted therapies have been approved by the FDA in the past 7 years for patients with metastatic RCC; however, all of these drugs have been associated with resistance

  • Even with targeted therapy, progression-free survival for patients with metastatic RCC rarely extends beyond 2 years

  • Biomarkers are needed for the early screening of patients at risk of RCC and the identification of novel therapeutic targets should accelerate the development of new or modified drugs

  • The key biofluid markers for RCC are 14-3-3 protein β/α, kidney injury molecule 1, quinolinate, aquaporin 1, adipophilin, and several microRNAs (all of which are non-RCC-specific)

  • Currently available targeted drugs include multikinase and mammalian target of rapamycin C1 inhibitors; programmed death 1, histone deacetylase, and chromosome region maintenance protein 1 inhibitors are in clinical trials

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Figure 1: Promising therapeutic targets for RCC.

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Acknowledgements

The work by R. H. Weiss was supported by National Institutes of Health grants 1R01CA135401-01A1 and 1R01DK082690-01A1, as well as the Medical Service of the US Department of Veterans' Affairs.

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  1. Division of Nephrology, University of California, Davis, 95616, CA, USA

    Hiromi I. Wettersten & Robert H. Weiss

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  1. Hiromi I. Wettersten
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H. I. Wettersten researched the literature for this article. R. H. Weiss and H. I. Wettersten contributed towards writing, discussing, and editing the manuscript.

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Correspondence to Robert H. Weiss.

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Wettersten, H., Weiss, R. Potential biofluid markers and treatment targets for renal cell carcinoma. Nat Rev Urol 10, 336–344 (2013). https://doi.org/10.1038/nrurol.2013.52

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