CONTEXT: There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer. OBJECTIVE: This review characterizes the metabolic effects of genes and signaling pathways commonly implicated in renal cancer. EVIDENCE ACQUISITION: A systematic review of the literature was performed using PubMed. The search strategy included the following terms: renal cancer, metabolism, HIF, VHL. EVIDENCE SYNTHESIS: Significant progress has been made in the understanding of the metabolic derangements present in renal cancer. These findings have been derived through translational, in vitro, and in vivo studies. To date, the most well-characterized metabolic features of renal cancer are linked to von Hippel-Lindau (VHL) loss. VHL loss and the ensuing increase in the expression of hypoxia-inducible factor affect several metabolic pathways, including glycolysis and oxidative phosphorylation. Collectively, these changes promote a glycolytic metabolic phenotype in renal cancer. In addition, other histologic subtypes of renal cancer are also notable for metabolic derangements that are directly related to the causative genes. CONCLUSIONS: Current knowledge of the genetics of renal cancer has led to significant understanding of the metabolism of this malignancy. Further studies of the metabolic basis of renal cell carcinoma should provide the foundation for the development of new treatment approaches and development of novel biomarkers.
CONTEXT: There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer. OBJECTIVE: This review characterizes the metabolic effects of genes and signaling pathways commonly implicated in renal cancer. EVIDENCE ACQUISITION: A systematic review of the literature was performed using PubMed. The search strategy included the following terms: renal cancer, metabolism, HIF, VHL. EVIDENCE SYNTHESIS: Significant progress has been made in the understanding of the metabolic derangements present in renal cancer. These findings have been derived through translational, in vitro, and in vivo studies. To date, the most well-characterized metabolic features of renal cancer are linked to von Hippel-Lindau (VHL) loss. VHL loss and the ensuing increase in the expression of hypoxia-inducible factor affect several metabolic pathways, including glycolysis and oxidative phosphorylation. Collectively, these changes promote a glycolytic metabolic phenotype in renal cancer. In addition, other histologic subtypes of renal cancer are also notable for metabolic derangements that are directly related to the causative genes. CONCLUSIONS: Current knowledge of the genetics of renal cancer has led to significant understanding of the metabolism of this malignancy. Further studies of the metabolic basis of renal cell carcinoma should provide the foundation for the development of new treatment approaches and development of novel biomarkers.
Authors: Swethajit Biswas; Philip J S Charlesworth; Gareth D H Turner; Russell Leek; Paul T Thamboo; Leticia Campo; Helen Turley; Petra Dildey; Andrew Protheroe; David Cranston; Kevin C Gatter; Francesco Pezzella; Adrian L Harris Journal: Carcinogenesis Date: 2012-07-09 Impact factor: 4.944
Authors: Michael J Leveridge; Antonio Finelli; John R Kachura; Andrew Evans; Hannah Chung; Daniel A Shiff; Kimberly Fernandes; Michael A S Jewett Journal: Eur Urol Date: 2011-06-24 Impact factor: 20.096
Authors: Ian P M Tomlinson; N Afrina Alam; Andrew J Rowan; Ella Barclay; Emma E M Jaeger; David Kelsell; Irene Leigh; Patricia Gorman; Hanan Lamlum; Shamima Rahman; Rebecca R Roylance; Simon Olpin; Stephen Bevan; Karen Barker; Nicholas Hearle; Richard S Houlston; Maija Kiuru; Rainer Lehtonen; Auli Karhu; Susa Vilkki; Päivi Laiho; Carita Eklund; Outi Vierimaa; Kristiina Aittomäki; Marja Hietala; Pertti Sistonen; Anders Paetau; Reijo Salovaara; Riitta Herva; Virpi Launonen; Lauri A Aaltonen Journal: Nat Genet Date: 2002-02-25 Impact factor: 38.330
Authors: Arun Sreekumar; Laila M Poisson; Thekkelnaycke M Rajendiran; Amjad P Khan; Qi Cao; Jindan Yu; Bharathi Laxman; Rohit Mehra; Robert J Lonigro; Yong Li; Mukesh K Nyati; Aarif Ahsan; Shanker Kalyana-Sundaram; Bo Han; Xuhong Cao; Jaeman Byun; Gilbert S Omenn; Debashis Ghosh; Subramaniam Pennathur; Danny C Alexander; Alvin Berger; Jeffrey R Shuster; John T Wei; Sooryanarayana Varambally; Christopher Beecher; Arul M Chinnaiyan Journal: Nature Date: 2009-02-12 Impact factor: 49.962
Authors: John D Gordan; Priti Lal; Vijay R Dondeti; Richard Letrero; Krishna N Parekh; C Elisa Oquendo; Roger A Greenberg; Keith T Flaherty; W Kimryn Rathmell; Brian Keith; M Celeste Simon; Katherine L Nathanson Journal: Cancer Cell Date: 2008-12-09 Impact factor: 31.743
Authors: James B Brugarolas; Francisca Vazquez; Archana Reddy; William R Sellers; William G Kaelin Journal: Cancer Cell Date: 2003-08 Impact factor: 31.743
Authors: Hyun-Wook Lee; Mary E Handlogten; Gunars Osis; William L Clapp; Dara N Wakefield; Jill W Verlander; I David Weiner Journal: Am J Physiol Renal Physiol Date: 2016-12-07
Authors: Roy Mano; A Ari Hakimi; Emily C Zabor; Marta A Bury; Olivio F Donati; Christoph A Karlo; Wassim M Bazzi; Helena Furberg; Paul Russo Journal: Can Urol Assoc J Date: 2014-09 Impact factor: 1.862
Authors: Maximilian Christian Kriegmair; Philipp Mandel; Stefan Porubsky; Julia Dürr; Nina Huck; Philipp Nuhn; Daniel Pfalzgraf; Maurice Stephan Michel; Nina Wagener Journal: Horm Cancer Date: 2017-02-28 Impact factor: 3.869
Authors: Shuyu Tang; Maxwell V Meng; James B Slater; Jeremy W Gordon; Daniel B Vigneron; Bradley A Stohr; Peder E Z Larson; Zhen Jane Wang Journal: Cancer Date: 2021-04-12 Impact factor: 6.860
Authors: Kevin D Courtney; Divya Bezwada; Tomoyuki Mashimo; Kumar Pichumani; Vamsidhara Vemireddy; Alexander M Funk; Jennifer Wimberly; Sarah S McNeil; Payal Kapur; Yair Lotan; Vitaly Margulis; Jeffrey A Cadeddu; Ivan Pedrosa; Ralph J DeBerardinis; Craig R Malloy; Robert M Bachoo; Elizabeth A Maher Journal: Cell Metab Date: 2018-08-23 Impact factor: 27.287