Modulation of glycolysis in neuroepithelial tumors.
Among the features of the reprogrammed neoplastic phenotype there is the metabolic property to display an increased glycolytic capacity and the ability to convert glucose to lactic acid in the presence of oxygen. Human gliomas in vivo and in vitro are capable to metabolize glucose in a way strictly related to the pathological degree of malignancy. The drug Lonidamine [1-(2,4-dichlorobenzyl)-1H-indazol-3 carboxylic acid)] (LND) is able to selectively block hexokinase (HK) activity and, consequently, lactate production only in highly glycolytic (highly malignant) gliomas, stimulating, on the contrary, that of low grade gliomas; this basically depends on the different HK patterns between low and high grade gliomas. LND is under clinical trial in order to evaluate its effectiveness in glioma therapy.
Floridi
A
A
Regina Elena Institute for Cancer Research, Rome, Italy.
Paggi
M G
MG
Fanciulli
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007191:Indazoles; D011720:Pyrazoles; D006593:Hexokinase; C016371:lonidamine