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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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Molecular Cancer

ISSN: 1476-4598