Dr. Weeks’ Comment:   the Warburg effect (a particular metabolic pathway in carcinomas characterized by the anaerobic degradation of glucose even in the presence of oxygen (aerobic glycolysis) that leads to the production of large amounts of lactate) has been know but not utilized for decades. Anti-oxidants and starving the cancer of its nourishment (glucose/sugar!) is a smart strategy. Corrective Cancer Care utilizes this Achilles heel of cancer. Primum non nocere!

 

 

Molecular Diagnostics

British Journal of Cancer (2006) 94, 578-585. doi:10.1038/sj.bjc.6602962 www.bjcancer.com
Published online 7 February 2006

Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted

S Langbein1,10,11, M Zerilli2,10, A zur Hausen3, W Staiger4, K Rensch-Boschert5, N Lukan4, J Popa1, M P Ternullo6, A Steidler1, C Weiss7, R Grobholz8, F Willeke4, P Alken1, G Stassi2, P Schubert9 and J F Coy5,9

Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactate-based matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.

Cancer is now viewed as a disease resulting from cancer-causing genes that deregulate cellular proliferation, differentiation, and death. Genetic alterations acquired by tumours also modify their biochemical pathways, resulting in abnormal metabolism. Warburg proposed a model of tumorigenesis involving altered energy production in tumours. He identified a particular metabolic pathway in carcinomas characterised by the anaerobic degradation of glucose even in the presence of oxygen (aerobic glycolysis) that leads to the production of large amounts of lactate (known as the Warburg effect; Warburg et al, 1924). The relevance of aerobic glycolysis to cancer cell biology remains controversial (Garber, 2004Gatenby and Gillies, 2004). However, the widespread clinical use of positron-emission tomography (PET) for the detection of aerobic glycolysis in tumours and recent findings have rekindled interest in Warburg’s theory. Studies on the physiological changes in malignant conversion provided a metabolic signature for the different stages of tumorigenesis (Ramanathan et al, 2005); during tumorigenesis, an increase in glucose uptake and lactate production have been detected. The fully transformed state is most dependent on aerobic glycolysis and least dependent on the mitochondrial machinery for ATP synthesis (Ramanathan et al, 2005).

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Dr. Weeks’ Comment:   the Warburg effect (a particular metabolic pathway in carcinomas characterized by the anaerobic degradation of glucose even in the presence of oxygen (aerobic glycolysis) that leads to the production of large amounts of lactate) has been know but not utilized for decades. Anti-oxidants and starving the cancer of its nourishment (glucose/sugar!)…
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