Renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery, whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in the treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitinib, which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and everolimus and temsirolimus, which inhibit mechanistic target of rapamycin complex 1 (mTORC1), being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies, such as nivolumab, have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the biology of RCC, with a focus on ccRCC, as well as updates to complement the current clinical guidelines and an outline of potential future directions for RCC research and therapy.

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Figure 1: Distinct subtypes of renal cell carcinoma.
Figure 2: Global kidney cancer incidence.
Figure 3: VHL inactivation in clear cell renal cell carcinoma and its implication in targeted therapy.
Figure 4: Cancer evolution and tumour heterogeneity in clear cell renal cell carcinoma.
Figure 5: Stages of kidney cancer and recommended treatments.
Figure 6: Indications for radical nephrectomy.
Figure 7: Therapeutic evolution and survival outcome of metastatic clear cell renal cell carcinoma through the four different eras.
Figure 8: Treatment algorithms for renal cell carcinoma.

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Acknowledgements

J.J.H. is supported by the J. Randall & Kathleen L. MacDonald Family Research Fund, the Tom and Mila Tuttle Family Research Fund, the Jill and Rafic Dahan Family Research Fund, and the Jill and Jeffrey Weiss Family Research Fund for the cure of metastatic kidney cancer. J.L. is supported by the National Institute of Health Research (NIHR) Royal Marsden/Institute of Cancer Research Biomedical Research Centre for Cancer. M.P.P. is supported by the Intramural Research Program of the National Cancer Institute, US National Institutes of Health.

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Introduction (J.J.H.); Epidemiology (M.P.P.); Mechanisms/pathophysiology (S.S., J.J.H. and C.S.); Diagnosis screening and prevention (L.A. and M.S.); Management (V.F. and J.L.); Quality of life (D.Y.H.); Outlook (J.J.H.); Overview of Primer (J.J.H.).

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Correspondence to James J. Hsieh.

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Competing interests

J.J.H. is a consultant for Novartis, Eisai and Chugai and has received research funding from Pfizer, Novartis, Eisai and Cancer Genomics Inc. C.S. is a consultant for Roche, Pfizer, Boehringer Ingelheim, Novartis, Celgene, Servler, Eli Lilly and GlaxoSmithKline, and owns stock options from Achilles Therapeutics, Epic Biosciences, Grail and ApoGen Biotech. L.A. is a consultant for Pfizer, Novartis, Sanofi, Amgen, Bristol-Myers Squibb, Bayer and Cerulean, and has received research funding from Pfizer and Novartis. M.S. is a consultant for Pfizer, Bristol-Myers Squibb, Ipsen, Exelixis, Eisai, Roche, Novartis and Astellas. D.Y.H. is a consultant for Pfizer, Novartis and Bristol-Myers Squibb. J.L. has received research funding from Novartis, Pfizer, Bristol-Myers Squibb and Merck Sharp & Dohme. M.P.P., S.S. and V.F. declare no competing interests.

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Hsieh, J., Purdue, M., Signoretti, S. et al. Renal cell carcinoma. Nat Rev Dis Primers 3, 17009 (2017). https://doi.org/10.1038/nrdp.2017.9

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