Table 1.

Drug Resistance Genes and Their Potential Use in Chemotherapy.

Gene and Localization	Resistance to	Mode of Action	Level of Evidence	References
Plasma membrane
MDR1* (P-glycoprotein 1)	Anthracyclines, vinca alkaloids, taxoids, etoposide	Efflux of drugs	Human xenotransplant model (human clinical trial)†	[17,74]
Multidrug resistance-related protein‡	Anthracyclines, vinca alkaloids, taxoids, etoposide	Efflux of drugs	Murine in vivo model	[75]
hENT2 nucleoside transporter	Trimetrexate, tomudex (plus NBMPR§)	Nucleoside transporter	Murine in vivo model	[76]
ABLG2¶	Anthracyclines, taxoids	Efflux of drugs (side population)	Human cell lines	[77]
Cytoplasmic
DHFR	Methotrexate, trimetrexate	Mutant form is unaffected by the drug	Large animal model	[78]
CDD	ara-C, gemcitabine	Detoxification of prodrug	Murine in vivo model	[39]
Aldehyde dehydrogenase	Cyclophosphamide	Detoxification of prodrug	Murine in vivo model	[79]
Glutathione S-transferase	Cyclophosphamide, anthracyclines	Detoxification of prodrug	Murine in vivo model	[80]
Thymidylate synthase	5-Fluorouracil, tomudex	Mutant form is unaffected by the drug	Murine primary cells	[81]
Ribonucleotide reductase	Hydroxyurea	Mutant form is unaffected by the drug	Murine in vivo model	[82,83]
Nuclear
MGMT#	Chloroethylnitrosoureas and decarbazine derivatives (plus BG)	Removal of O6 adducts from the DNA	Human clinical trial	[11]
APN1(yeast)/APE(human)**	Bleomycin and ionizing radiation	Repairs AP sites, oxidative damage, and alkylation damage in DNA	Human cell lines	[84,85]
8-Oxoguanine glycosylase/Fapy-DNA glycosylase	ThioTEPA	Removal of alkylated bases in DNA	Murine primary cells/murine in vivo model	[86]
Superoxide dismutase	Anthracyclines and paraquat	Protection against oxidative damage	Human cell lines	[75,87]
Topoisomerase I	Camptothecin	DNA repair function	Human cell lines	[78]
Topoisomerase II	Anthracyclines and etoposide	DNA repair function	Human cell lines	[79]
HPRT††	6-Thioguanine	Ribosylation of purine analogs	Murine in vivo model	[88]

^*Multidrug resistance gene.

^†Failed due to technical problems.

^‡Multidrug resistance-related protein coding gene.

^§Nitrobenzylmercaptopurine riboside.

^¶ATP-binding cassette subfamily G member 2 (also known as breast cancer resistance protein).

^#O₆-Methylguanine DNA-methyltransferase.

^**Apurinic/apyrimidinic endonuclease.

^††Hypoxanthine-guanine phosphoribosyl transferase.