1. Basic Research in Kidney Cancer
Egbert Oosterwijk, W. Kimryn Rathmell, Kerstin Junker, A. Rose Brannon, Frédéric Pouliot, David S. Finley, Peter F.A. Mulders, Ziya Kirkali, Hirotsugo Uemura, Arie Belldegrun 
European Urology 
Volume 60, Issue 4, Pages (October 2011)
DOI: /j.eururo
Copyright © 2011 European Association of Urology Terms and Conditions

2. Fig. 1
Schematic representation of the nephron and the different subtypes of renal cell carcinoma (RCC) according to the Heidelberg classification in relation to their positions within the nephron and collecting tubule. Genetic changes characteristic for the different RCC subtypes are indicated.
European Urology  , DOI: ( /j.eururo )
Copyright © 2011 European Association of Urology Terms and Conditions

3. Fig. 2
Schematic overview of relevant pathways in clear cell renal cell carcinoma (ccRCC) and targeted therapies. Under normal conditions, hypoxia inducible factor (HIF) α is constitutively degraded. HIFs bind to von Hippel-Lindau (VHL) protein, which is part of an E3 ubiquitin ligase complex that targets the protein for proteolysis. When the VHL gene is mutated, interaction between HIF and the VHL protein is disrupted, leading to stabilization/accumulation of HIF transcription factors. Under hypoxic conditions, the interaction between VHL and HIF is lost because specific proline residues in HIF are not hydroxylated, also leading to loss of interaction. HIF accumulation can also result from activation of mammalian target of rapamycin (mTOR) downstream of cellular stimuli and the PI3-K/Akt pathway. Accumulated HIF translocates into the nucleus leading to transcription of a large number of hypoxia inducible genes including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). These bind to their receptors present on the surface of endothelial cells, leading to (neo)vascularization. Temsirolimus and everolimus inhibit the kinase activity of the mTOR complex 1 (mTORC1); bevacizumab is a VEGF ligand-binding antibody; sunitinib, sorafenib, axitinib, and pazopanib are small molecule inhibitors of multiple tyrosine kinase receptors including VEGF-R and PDGFR.
European Urology  , DOI: ( /j.eururo )
Copyright © 2011 European Association of Urology Terms and Conditions