Metabolism of kidney cancer: from the lab to clinical practice.
BACKGROUND
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.


METHODS
A systematic review of the literature was performed using PubMed. The search strategy included the following terms: renal cancer, metabolism, HIF, VHL.


RESULTS
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.
Department of Urology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. sudarshan@uab.edu
Sunil
S
Sudarshan
Jose A
JA
Karam
James
J
Brugarolas
R Houston
RH
Thompson
Robert
R
Uzzo
Brian
B
Rini
Vitaly
V
Margulis
Jean-Jacques
JJ
Patard
Bernard
B
Escudier
W Marston
WM
Linehan
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D015398:Signal Transduction; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C497446:VHL protein, human