The role of drug-metabolizing enzymes in synthetic lethality of cancer

ElsevierVolume 240, December 2022, 108219Pharmacology & TherapeuticsAbstract

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.

Keywords

Drug metabolizing enzymes (DMEs)

Tumor progression

Drug discovery

Cancer therapy

Synthetic lethality

AbbreviationsALDH

aldehyde dehydrogenases

ALL

acute lymphoblastic leukemia

AML

acute myelogenous leukemia

ASS1

argininosuccinate synthase 1

AZQ

2,5-bis(carboethoxyamino)-3,6-diaziridinyl1,4-benzoquinone

DME

Drug metabolizing enzyme

FMO

flavin-dependent monooxygenase

GST

glutathione transferase

HR

homologous recombination

MATP

methylthioadenosine phosphorylase

MTA

S-methyl-5′-thioadenosine

NQO1

NAD[P] quinone oxidoreductase 1

PDAC

pancreatic ductal adenocarcinoma

PTC

papillary thyroid cancer

ROS

reactive oxygen species

TME

Tumor microenvironment

TPMT

Thiopurine S-methyltransferase

UGT

UDP-glucuronosyl transferase

siRNA

small interfering RNA

View full text

© 2022 Published by Elsevier Inc.

留言 (0)

沒有登入
gif