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The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease

Nature Reviews Nephrology volume 11, pages 515–534 (2015)Cite this article

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Key Points

  • For over a decade, the 'hallmarks of cancer' have provided a unifying framework for the complex set of cell, tissue and organismal defects associated with malignancy

  • Autosomal dominant polycystic kidney disease (ADPKD) is a relatively common inherited disorder with pathological features that echo those found in cancer

  • A systematic evaluation of ADPKD in the context of the ten cancer hallmarks emphasizes a surprising degree of similarity in signalling defects associated with the disease

  • Two key signalling processes involved in ADPKD—ciliary signalling and control of Ca2+/cAMP and polarized secretion—are not currently thought to be hallmarks of cancer

  • The pattern of conserved and distinct signalling pathways emphasizes important issues relevant to the optimal treatment of patients with ADPKD

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a progressive inherited disorder in which renal tissue is gradually replaced with fluid-filled cysts, giving rise to chronic kidney disease (CKD) and progressive loss of renal function. ADPKD is also associated with liver ductal cysts, hypertension, chronic pain and extra-renal problems such as cerebral aneurysms. Intriguingly, improved understanding of the signalling and pathological derangements characteristic of ADPKD has revealed marked similarities to those of solid tumours, even though the gross presentation of tumours and the greater morbidity and mortality associated with tumour invasion and metastasis would initially suggest entirely different disease processes. The commonalities between ADPKD and cancer are provocative, particularly in the context of recent preclinical and clinical studies of ADPKD that have shown promise with drugs that were originally developed for cancer. The potential therapeutic benefit of such repurposing has led us to review in detail the pathological features of ADPKD through the lens of the defined, classic hallmarks of cancer. In addition, we have evaluated features typical of ADPKD, and determined whether evidence supports the presence of such features in cancer cells. This analysis, which places pathological processes in the context of defined signalling pathways and approved signalling inhibitors, highlights potential avenues for further research and therapeutic exploitation in both diseases.

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Figure 1: A comparison of the pathological features of ADPKD and kidney cancer.
Figure 2: Signalling and drug targets relevant to the pathogenesis of ADPKD and kidney cancer.

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Acknowledgements

We apologize to those of our colleagues whose work we were unable to cite because of reference limits. We are very grateful to Dr James Calvet and Dr Jared Grantham (University of Kansas Medical Center, USA), who generously provided many useful suggestions and comments on the manuscript. We also thank the reviewers of this article for their valuable critiques. The authors were supported by funding from the PKD Foundation and DOD PRMRP W81XWH-12-1-0437/PR110518 (to E.A.G.), from the German Research Foundation SE2280/3-1, Köln Fortune 252/2013 and by the German Ministry of Science and Education (BMBF) as part of the MILES consortium (grant 01ZX1406) (to T.S.-N.), Pfizer independent grant #11703,561 (to D.M.G.), BE2212, SFB829, SFB832 (to T.B.), and by NIH Core Grant CA06927 (to Fox Chase Cancer Center).

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Authors and Affiliations

  1. Department I of Internal Medicine and Centre for Integrated Oncology, University of Cologne, Kerpenerstrasse 62, Cologne, D-50937, Germany

    Tamina Seeger-Nukpezah

  2. Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, 19111, PA, USA

    Daniel M. Geynisman

  3. Department of Developmental Therapeutics, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, 19111, PA, USA

    Anna S. Nikonova & Erica A. Golemis

  4. Department II of Internal Medicine and Centre for Molecular Medicine Cologne, University of Cologne, Kerpenerstrasse 62, Cologne, D-50937, Germany

    Thomas Benzing

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Contributions

T.S.-N., D.M.G., A.S.N. and E.A.G. researched data for the article. T.S.-N., D.M.G., and E.A.G. wrote the article. T.B. and A.S.N. contributed to the discussion and helped edit the manuscript for submission.

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Correspondence to Erica A. Golemis.

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Seeger-Nukpezah, T., Geynisman, D., Nikonova, A. et al. The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease. Nat Rev Nephrol 11, 515–534 (2015). https://doi.org/10.1038/nrneph.2015.46

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