For example, leukemic cells, although residing within the blood stream at
high oxygen tension, exhibit the Warburg effect
Esta dependncia por glucose a base para a imagem clnica de cancros
metsticos, atravs da aplicao da PET (FDH-PET).
Grande consumo de glucose est relacionado com a agressividade do tumor
e um mau prognstico.
Angiogenesis is the physiological process through which new blood vessels form from
pre-existing vessels.
Controlo da
gliclise:
(1.)
Glucose is phosphorylated by HK which has four isoenzymes; at
least one of which (type II) is over-expressed in cancers.
Therapeutically, HK has been targeted with the non-metabolised glucose
analog, 2-deoxyglucose (2-DG), which entered clinical trials for treatment
of advanced lung, breast, prostate and gastric cancers and others such
as 5-thioglucose and mannoheptulose. Another drug that was thought to
block HK but may actually target glyceraldehyde-3-phosphate
dehydrogenase is 3-bromopyruvate, which causes severe depletion of
cellular ATP with significant anti-cancer effect in vivo.
Lonidamine, a derivative of indazole-3-carboxylic acid inhibits both
oxidative phosphorylation and the Warburg effect through interaction
with a mitochondrial bound HK - FDA approval is currently withdrawn due
to occurrence of liver problems.
(2.)
PFK is the second important rate limiting enzyme in glycolysis
and could potentially be a very effective target