Table 1.

Key metabolic genes and related metabolites from the nucleotide metabolism in cancer immunity

Key metabolic genes	Involved metabolic module	Metabolic substrate	Metabolic product	Therapeutic agents	References
Nucleotide metabolism
NT5E (CD73)	Purine nucleobase metabolism, pyrimidine nucleobase metabolism, adenosine biosynthesis, AMP catabolic process, DNA metabolic process, purine nucleotide biosynthesis	Phosphated ribonucleoside	Ribonucleoside	Oleclumab, AB680, APCP	[21, 22]
ENTPD1(CD39)	Purine metabolism, Pyrimidine metabolism	Phosphated ribonucleoside	Phosphated ribonucleoside	TTX-030, IPH5201	[21, 23, 24]
PNP	Purine-nucleoside phosphorylase activity	Ribonucleoside	Phosphated ribonucleoside	Forodesine	[25–27]
Purine metabolism
ADSS	Adenine ribonucleotide biosynthesis	IMP	ADP, ATP		[28]
ADA	Purine metabolism	Adenosine	Inosine	Elapegademase, pentostatin	[29]
XDH	Purine metabolism	Hypoxanthine, Xanthine	Xanthine, uric acid	Allopurinol, amflutizole	[30]
PPAT	5-Phosphoribosylamine biosynthesis	PRPP	5-Phosphoribosylamine and pyrophosphate	D-pantetheine 4'-phosphate	[31]
PRPS	PRPP biosynthesis	Ribose 5P	PRPP		[32, 33]
GART	Inosine monophosphate biosynthesis	PRPP	IMP	Lometrexol sodium, Pelitrexol, Pemetrexed	[34, 35]
IMPDH	Guanine ribonucleotide biosynthesis	IMP	GDP, GTP	Merimepodib, mizoribine, mycophenolic acid	[36–40]
Pyrimidine metabolism
CAD	Uridine monophosphate biosynthesis	Glutamine	UMP		[41, 42]
DHODH	Uridine monophosphate biosynthesis	Dihydroorotate	Orotate	Brequinar sodium, leflunomide, and teriflunomide	[43–46]
UMPS	Uridine monophosphate biosynthesis	Glutamine	UMP		[8, 42, 47]
DPYD	Pyrimidine degradation	Uracil, thymine	Beta-alanine, 3-aminoisobutanoate	Eniluracil, Gimeracil	[48–50]
CDD	Uridine monophosphate synthesis	Cytidine, Deoxycytidine	Uridine, Deoxyuridine		[51, 52]

APCP adenosine 5'-(alpha, beta-methylene) diphosphate