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Unique Opportunity for Disease-based Therapy
Article first published online: 28 APR 2009
Published 2009 American Cancer Society
Supplement: Innovations and Challenges in Renal Cancer: Proceedings of the Third Cambridge Conference, Supplement to Cancer
Volume 115, Issue Supplement 10, pages 2252–2261, 15 May 2009
How to Cite
Linehan, W. M., Pinto, P. A., Bratslavsky, G., Pfaffenroth, E., Merino, M., Vocke, C. D., Toro, J. R., Bottaro, D., Neckers, L., Schmidt, L. S. and Srinivasan, R. (2009), Hereditary kidney cancer. Cancer, 115: 2252–2261. doi: 10.1002/cncr.24230
This article is US Government work and, as such, is in the public domain in the United States of America.
This educational proceedings publication is based on a symposium held on June 27-28, 2008, in Cambridge, Massachusetts.
- Issue published online: 28 APR 2009
- Article first published online: 28 APR 2009
- Manuscript Accepted: 10 DEC 2008
- Manuscript Revised: 3 DEC 2008
- Manuscript Received: 18 SEP 2008
- Genentech, Novartis Pharmaceuticals, Pfizer, Inc., and Wyeth Pharmaceuticals
- National Institutes of Health, National Cancer Institute, Center for Cancer Research
- National Cancer Institute, National Institutes of Health. Grant Number: N01-CO-12,400
- von Hippel-Lindau;
- fumarate hydratase
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 VHL gene is the gene for the hereditary cancer syndrome, von Hippel-Lindau, as well as for the common form of sporadic, noninherited, clear cell kidney cancer. Understanding the VHL-hypoxia 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 MET, the cell surface receptor for hepatocyte growth factor. Mutations of MET also have been identified in a subset of tumors from patients with sporadic type 1 papillary renal cell carcinoma (RCC). Clinical trials targeting the MET pathway are currently underway in patients with HPRC and in patients with sporadic (nonhereditary) papillary kidney cancer. The BHD gene (also known as folliculin or FLCN) is the gene for Birt-Hogg-Dube syndrome, an autosomal-dominant 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-Hogg-Dube 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-HIF pathways have provided the foundation for therapeutic approaches in patients with HLRCC-associated kidney cancer as well as other hereditary and sporadic forms of RCC. Cancer 2009;115(10 suppl):2252-61. Published 2009 by the American Cancer Society.