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Nat Rev Dis Primers. 2017 Mar 9;3:17009. doi: 10.1038/nrdp.2017.9.

Renal cell carcinoma.

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Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8069, St. Louis, Missouri 63110, USA.
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Francis Crick Institute, UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, London, UK.
Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France.
Department of Medicine I, Clinical Division of Oncology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Department of Medical Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
Department of Medical Oncology, Royal Marsden NHS Foundation Trust, London, UK.
Department of Experimental and Clinical Medical Sciences - Urologic Clinic, University of Udine, Udine, Italy.


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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