Metástases e metabolismo

Int. J. Cancer: 122, 2422–2428 (2008) ' 2008 Wiley-Liss, Inc.

Metastasis is promoted by a bioenergetic switch: New targets for progressive renal cell cancer
Sigrun Langbein1*, Wilma M. Frederiks2, Axel zur Hausen3, Juljane Popa4, Jan Lehmann5, Christel Weiss6, Peter Alken4 and Johannes F. Coy7 1 Department of Urology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands 2 Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands 3 Institute of Pathology, Ludwig-Aschoff-Haus, University of Freiburg, Freiburg, Germany 4 Department of Urology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany 5 Department of Urology, Municipal Hospital Kiel, Chemnitzstr. 33, Kiel, Germany 6 Department of Biostatistics, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany 7 Department of Obstetrics and Gynecology, University of Wuerzburg, Wuerzburg, Germany
Targeted therapies have demonstrated clinical benefit with limited impact on long-term disease specific survival in the treatment of renal cell cancer (RCC). New opportunities for the treatment of tumors that are resistant or have relapsed, are needed. Increased anaerobic glucose fermentation to lactate (aerobic glycolysis), leading to oxygen- and mitochondria-independent ATP generation is a hallmark of aggressive cancer growth. This metabolic shift results in increased lactate production via cycling through the pentose phosphate pathway (PPP), and plays an important role in tumor immune escape, progression and resistance to immune-, radiation- and chemo-therapy. This study explored the activity and impact of the oxidative and nonoxidative branches of the PPP on RCC to evaluate new therapeutic options. Activity was determined in the oxidative branch by glucose-6-phosphate-dehydrogenase (G6PD) activity, and in the nonoxidative branch by the total