Drug-metabolizing enzymes (DMEs) have shown increasing importance in anticancer therapy. It is not only due to their effect on activation or deactivation of anticancer drugs, but also because of their extensive connections with pathological and biochemistry changes during tumorigenesis. Meanwhile, it has become more accessible to discovery anticancer drugs that selectively targeted cancer cells with the development of synthetic lethal screen technology. Synthetic lethal strategy makes use of unique genetic markers that different cancer cells from normal tissues to discovery anticancer agents. Dysregulation of DMEs has been found in various cancers, making them promising candidates for synthetic lethal strategy. In this review, we will systematically discuss about the role of DMEs in tumor progression, the application of synthetic lethality strategy in drug discovery, and a link between DMEs and synthetic lethal of cancer.
KeywordsDrug metabolizing enzymes (DMEs)
Tumor progression
Drug discovery
Cancer therapy
Synthetic lethality
AbbreviationsALDHaldehyde dehydrogenases
ALLacute lymphoblastic leukemia
AMLacute myelogenous leukemia
ASS1argininosuccinate synthase 1
AZQ2,5-bis(carboethoxyamino)-3,6-diaziridinyl1,4-benzoquinone
DMEDrug metabolizing enzyme
FMOflavin-dependent monooxygenase
GSTglutathione transferase
HRhomologous recombination
MATPmethylthioadenosine phosphorylase
MTAS-methyl-5′-thioadenosine
NQO1NAD[P] quinone oxidoreductase 1
PDACpancreatic ductal adenocarcinoma
PTCpapillary thyroid cancer
ROSreactive oxygen species
TMETumor microenvironment
TPMTThiopurine S-methyltransferase
UGTUDP-glucuronosyl transferase
siRNAsmall interfering RNA
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