{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:32:07Z","timestamp":1790253127670,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"S10","license":[{"start":{"date-parts":[[2009,4,28]],"date-time":"2009-04-28T00:00:00Z","timestamp":1240876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Genentech, Novartis Pharmaceuticals, Pfizer, Inc., and Wyeth Pharmaceuticals"},{"name":"National Institutes of Health, National Cancer Institute, Center for Cancer Research"},{"name":"National Cancer Institute, National Institutes of Health","award":["N01-CO-12,400"],"award-info":[{"award-number":["N01-CO-12,400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2009,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Kidney cancer is not a single disease; it is comprised of several different types of cancer, each with a different histology, with a different clinical course, caused by a different gene, and responding differently to therapy. The <jats:italic>VHL<\/jats:italic> gene is the gene for the hereditary cancer syndrome, von Hippel\u2010Lindau, as well as for the common form of sporadic, noninherited, clear cell kidney cancer. Understanding the VHL\u2010hypoxia inducible factor (HIF) pathway has provided the foundation for the development of several agents targeting this pathway, such as sunitinib, sorafenib, and temsirolimus. Hereditary papillary renal carcinoma (HPRC) is a hereditary renal cancer syndrome in which affected individuals are at risk for the development of bilateral, multifocal, type 1 papillary renal cell carcinoma. The genetic defect underlying HPRC is <jats:italic>MET<\/jats:italic>, the cell surface receptor for hepatocyte growth factor. Mutations of <jats:italic>MET<\/jats:italic> also have been identified in a subset of tumors from patients with sporadic type 1 papillary renal cell carcinoma (RCC). Clinical trials targeting the <jats:italic>MET<\/jats:italic> pathway are currently underway in patients with HPRC and in patients with sporadic (nonhereditary) papillary kidney cancer. The <jats:italic>BHD<\/jats:italic> gene (also known as folliculin or <jats:italic>FLCN<\/jats:italic>) is the gene for Birt\u2010Hogg\u2010Dube syndrome, an autosomal\u2010dominant genodermatosis associated with a hereditary form of chromophobe and oncocytic, hybrid RCC. Preclinical studies are underway targeting the BHD gene pathway in preparation for clinical trials in Birt\u2010Hogg\u2010Dube and sporadic chromophobe RCC. Patients with hereditary leiomyomatosis RCC (HLRCC) are at risk for developing cutaneous and uterine leiomyomas and a very aggressive type of RCC. HLRCC is characterized by germline mutation of the Krebs cycle enzyme, fumarate hydratase (FH). Studies of the tricarboxylic acid cycle and the VHL\u2010HIF pathways have provided the foundation for therapeutic approaches in patients with HLRCC\u2010associated kidney cancer as well as other hereditary and sporadic forms of RCC. Cancer 2009;115(10 suppl):2252\u201061. Published 2009 by the American Cancer Society.<\/jats:p>","DOI":"10.1002\/cncr.24230","type":"journal-article","created":{"date-parts":[[2010,3,2]],"date-time":"2010-03-02T12:47:25Z","timestamp":1267534045000},"page":"2252-2261","source":"Crossref","is-referenced-by-count":88,"title":["Hereditary kidney cancer"],"prefix":"10.1002","volume":"115","author":[{"given":"W. 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