The relevance of tyrosine kinase inhibitors for global metabolic pathways in cancer

Table 1 Summary of key metabolites and molecules affected by TKIs in cancer. Up- or downregulation highly depends on the inhibitor and model of the study used

Metabolite	Function in	Sense of Regulation	Rerence(s)
Fructose 1,6-bisphosphate	glycolysis	↓	[27, 34, 38, 41, 45, 48, 49, 58]
Dihydroxyacetone phosphate
3-phosphoglycerate
Glucose (consumption)
Phosphoenolpyruvate	glycolysis and gluconeogenesis	↓	[22, 27, 38, 45]
Lactate
Glyceraldehyde 3-phosphate
Pyruvate
6-phosphogluconate	pentose phosphate pathway	↓	[27, 58]
Ribulose-5-phosphate
Ribose-5-phosphate
Xylulose-5-phosphate
D-sedoheptulose 1,7-bisphosphate	pentose phosphate pathway	↑	[34]
Deoxyribose phosphate	pentose phosphate pathway	↑	[34]
Glucose-6-phosphate	glycolysis and PPP	↓	[27, 58]
Glutamate	amino acid metabolism	↑	[27, 30, 34, 45, 74]
Valine
Lysine
Tyrosine
Aspartate
Proline
Threonine
Histidine
Asparagine
Tryptophan
Alanine
NADPH	pentose poshosphate pathway	↓	[34, 51]
NADPH	oxidation-reduction pathways	↓	[34, 51]
ATP, GTP, CTP, TTP	energy metabolism	↑	[32, 45, 58]
Fumarate	TCA cycle	↓	[27, 30]
Malate
Citrate
Arginine	amino acid metabolism	↓	[74, 76]
Citrate	TCA cycle	↑	[32]
ATP	energy metabolism	↓	[60, 62]
Phosphocholine	glycerophospholipid metabolism	↓	[45, 87,88,89]

Abbreviations: ↑—Up-regulation; ↓—Down-regulation; TCA cycle Tricarboxylic acid cycle; NADPH Nicotinamide adenine dinucleotide phosphate; ATP Adenosine triphosphate; GTP Guanosine triphosphate; CTP Cytidine triphosphate; TTP Thymidine triphosphate

ISSN: 1476-4598