title: 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.
authors.affiliation: 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.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: Francis Crick Institute, UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, London, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
authors.affiliation: Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Department of Medicine I, Clinical Division of Oncology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidinger
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Heng
authors.affiliation: Department of Medical Oncology, Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.affiliation: Department of Experimental and Clinical Medical Sciences - Urologic Clinic, University of Udine, Udine, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
mesh_terms: D000077784:Axitinib; D000068258:Bevacizumab / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000150:complications* / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007191:Indazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007668:Kidney / Q000033:anatomy & histology; D007674:Kidney Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D011788:Quality of Life / Q000523:psychology; D012307:Risk Factors; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000819:agonists / Q000627:therapeutic use
chemical_list: D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; C516667:pazopanib; D000077157:Sorafenib; D000077784:Axitinib; D000077210:Sunitinib