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!
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.