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Table 1 Therapeutic targets

From: The metabolic advantage of tumor cells

Targets Metabolic pathway Activity Drugs: inhibitors or activators References
1 Proteolysis/alanine/transaminase/pyruvate increased aminooxacetic, 2PAM, D alanine, β chloro-L-alanine [42, 43]
2 Lactate dehydrogenase/pyruvate/lactate/NAD+ Malate dehydrogenase/OAA/malate/NAD+ Malic enzyme/malate/pyruvate/lactate/NAD+ increased increased increased Br pyruvate, gossypol D malate, humic acid D malate [44–46]
3 Glycolysis increased mannoheptulose, lodinamineepalresta, citrate [47–49]
4 PEP carboxykinase/PEP/OAA Pyruvate carboxylase/pyruvate/OAA increased decreased Cl-PEP, β sulphopyruvate 3-hydroxybutyrate (ketone bodies will activate) [50, 51] [52]
5 Pyruvate kinase (M2 bottleneck)/PEP/pyruvate Pyruvate dehydrogenase/pyruvate/acetylCoA decreased decreased dihydroxyphenylethanol, polyethylene - glycol lipoic acid, kinase inhibitors (dichloroacetate, 2-chloropropionate) or PP2A agonists (xylulose5P, B12, choline) [53–55] [16, 17]
6 Lipolytic fatty acid source of acetyl CoA Carnitine transporter increased niacine, Growth hormone inhibitors Avoid oxfenicine or levofloxacin [56, 57]
7 Citrate synthase (OAA+ acetylCoA)/citrate increased Dserine, fluoroacetylCoA, carboxymethyl-CoA, citrate (via product inhibition), capsaicine (via electron transport inhibition and NADH increase) [13]
8 ATPcitrate lyase citrate/OAA+acetylCoA Triglycerides synthesis via acetyl CoA Other OAA sources increased increased increased hydroxycitrate, fluorocitrate xanthohumol (removes triglycerides) D malate [58] [59]
9 Choline dehydrogenase/methylation/lipotropic Choline kinase/phosphorylcholine/lecithin decreased increased choline miltefosin, farnesol [60, 61]
10 PP2A methylation (it counteracts signaling and enzyme kinases) decreased betaine, folate, B12, trimethylglycine (via SAM)  
11 Histone deacetylase (gene silencing) increased butyrate, valproate, benzamide, trichostatin [62]
12 Cytochrome P450 demethylase (hypomethylated promoters)HAT/hexokinase expression Histone acetylase increased increased ketonazole, bergamottin, quinine anacardic acid, garcinol, curcumine [63–67] [66, 67]
13 Tyrosine kinase-signaling route (MAP kin, PI3 kin, PLCγ) increased imatinib mésilate (glivec chemotherapy)  
14,15, 16 GH-IGF IGFBP increased decreased octreotide, pegvisomant apigenin, casodex, omeprazol [68–70]
17 Arginine dependency increased arginine deprivation diet, pegylated arginine deiminase [18–20] [71–73]
18 Arginase/arginine/ornithine increased norvaline, N-omega-hydroxy-nor-arginine, boroargininre [74–76]
19 Polyamine pathway: Ornithine decarboxylase/putrescine SAM decarboxylase increased DFMO (2-difluoromethylornithine), MGBG methylglyoxal bis (guanylhydrazone), 4-amidinoindan-1one-2'-amidinhydrazone(alfa-fluoromethylhistidine) [77–79]
20 Glutaminase/glutamate increased DON(6-diazo-5-oxo-l-norleucine), riluzole, naftazone [80].
21 Argininosuccinate synthetase decreased troglitazone [81]
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