The VHL/HIF Axis in Clear Cell Renal Carcinoma
Chuan Shen,William G. Kaelin +1 more
TLDR
Deregulation of HIF2α appears to be a driving force in pVHL-defective clear cell renal carcinomas, and genetic and functional studies suggest that HIF1α serves as a tumor suppressor and is a likely target of the 14q deletions that are characteristic of this tumor type.About:
This article is published in Seminars in Cancer Biology.The article was published on 2013-02-01 and is currently open access. It has received 311 citations till now. The article focuses on the topics: HIF1A & Ubiquitin ligase complex.read more
Citations
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Journal ArticleDOI
Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma
Toni K. Choueiri,Bernard Escudier,Thomas Powles,Paul N. Mainwaring,Brian I. Rini,Frede Donskov,Hans J. Hammers,Thomas E. Hutson,Jae-Lyun Lee,Katriina Peltola,Bruce J. Roth,Georg A. Bjarnason,Lajos Géczi,Bhumsuk Keam,Pablo Maroto,Daniel Y.C. Heng,Manuela Schmidinger,Philip W. Kantoff,Anne E. Borgman-Hagey,Colin Hessel,Christian Scheffold,Gisela Schwab,Nizar M. Tannir,Robert J. Motzer +23 more
TL;DR: Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.
Journal ArticleDOI
Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial
Toni K. Choueiri,Bernard Escudier,Thomas Powles,Nizar M. Tannir,Paul N. Mainwaring,Brian I. Rini,Hans J. Hammers,Frede Donskov,Bruce J. Roth,K. Peltola,Jae-Lyun Lee,Daniel Y.C. Heng,Manuela Schmidinger,Neeraj Agarwal,Cora N. Sternberg,David F. McDermott,Dana T. Aftab,Colin Hessel,Christian Scheffold,Gisela Schwab,Thomas E. Hutson,Sumanta K. Pal,Robert J. Motzer +22 more
TL;DR: The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment.
Journal ArticleDOI
Hypoxia-Inducible Factors: Master Regulators of Cancer Progression
Luana Schito,Gregg L. Semenza +1 more
TL;DR: The current understanding of the consequences of HIF activity and the translational potential of targeting HIFs for cancer therapy are discussed.
Journal ArticleDOI
Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement
TL;DR: These findings reveal a tumor-suppressive role for specific tRNA-derived fragments and describe a molecular mechanism for their action, which may generalize to other tRNA, ribosomal-RNA, and sno-RNA fragments.
Journal ArticleDOI
Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity.
TL;DR: Hereditary pheochromocytomas and paragangliomas are powerful models for recognizing cancer driver events, which can be harnessed for diagnostic purposes and for guiding the future development of targeted therapies.
References
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Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.
Robert J. Motzer,Thomas E. Hutson,Piotr Tomczak,M. Dror Michaelson,Ronald M. Bukowski,Olivier Rixe,Stéphane Oudard,Sylvie Negrier,Cezary Szczylik,Sindy T. Kim,Isan Chen,Paul Bycott,Charles M. Baum,Robert A. Figlin +13 more
TL;DR: Progression-free survival was longer and response rates were higher in patients with metastatic renal-cell cancer who received sunitinib than in those receiving interferon alfa.
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Targeting of HIF-alpha to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,David R. Mole,Ya-Min Tian,Michael I. Wilson,Janine Gielbert,Simon J. Gaskell,Alex von Kriegsheim,Holger F. Hebestreit,Mridul Mukherji,Christopher J. Schofield,Patrick H. Maxwell,Christopher W. Pugh,Peter J. Ratcliffe +12 more
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Patrick H. Maxwell,Michael S. Wiesener,Gin-Wen Chang,Steven C. Clifford,Emma C. Vaux,Matthew Edward Cockman,Charles C. Wykoff,Christopher W. Pugh,Eamonn R. Maher,Peter J. Ratcliffe,Peter J. Ratcliffe +10 more
TL;DR: It is indicated that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF α-subunits, which may underlie the angiogenic phenotype of VHL-associated tumours.
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Sorafenib in advanced clear-cell renal-cell carcinoma.
Bernard Escudier,Tim Eisen,Walter M. Stadler,Cezary Szczylik,Stéphane Oudard,Michael Siebels,Sylvie Negrier,Christine Chevreau,Ewa Solska,Apurva A. Desai,Frederic Rolland,Tomasz Demkow,Thomas E. Hutson,Martin Gore,Scott Freeman,Brian Schwartz,M. Shan,Ronit Simantov,Ronald M. Bukowski +18 more
TL;DR: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects.
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing
Mircea Ivan,Keiichi Kondo,Haifeng Yang,William Y. Kim,Jennifer Valiando,Michael Ohh,Adrian Salic,John M. Asara,William S. Lane,William G. Kaelin,William G. Kaelin +10 more
TL;DR: It is found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated, which may play a key role in mammalian oxygen sensing.
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