Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)
Kidney cancer is one of the ten most common cancers in the United States. Approximately 75 % of kidney cancers are clear cell renal carcinomas, and most clear cell renal carcinomas are linked to inactivation of the von Hippel-Lindau tumor suppressor gene (VHL). Studies of the VHL gene product, pVHL, revealed that it participates in the oxygendependent degradation of the HIF (hypoxia-inducible factor) transcription factor. HIF is a master regulator of genes, such as vascular endothelial growth factor (VEGF), that participate in adaptation to hypoxia. The mTOR kinase also affects HIF protein and may also participate in signaling downstream of VEGF. Collectively these discoveries provided a conceptual framework for the testing, and eventual approval, of VEGF inhibitors and mTOR inhibitors for the treatment of kidney cancer. This chapter will review the molecular biology of kidney cancer, focusing on the role of pVHL in clear cell renal carcinoma.
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