Arginase: An emerging and promising therapeutic target for cancer treatment

Arginase is a key hydrolase in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. Increasing number of studies in recent years demonstrate that two mammalian arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), were aberrantly upregulated in various types of cancers, and playe...

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Bibliographic Details
Published in:	Biomedicine & pharmacotherapy Vol. 149; p. 112840
Main Authors:	Niu, Fanglin, Yu, Yi, Li, Zhuozhuo, Ren, Yuanyuan, Li, Zi, Ye, Qiang, Liu, Ping, Ji, Chenshuang, Qian, Lu, Xiong, Yuyan
Format:	Journal Article
Language:	English
Published:	France Elsevier Masson SAS 01-05-2022 Elsevier
Subjects:	Animals Arginase Arginase - metabolism Arginine - metabolism Cancer Inhibitors L-arginine Mammals Mechanism Neoplasms - drug therapy Therapeutic target Tumor Microenvironment Urea JNK ALT H. pylori CDK L-arginine UC Therapeutic target ODC mSHMT NF-κB IFN-γ PI3K mRCC ERK5 mTOR iNOS p38 MAPKs AML ARG2 PBT ARG1 TSC HNSCCs IL-4 DMBA IL-3 IL-1β MAPK PBMC EMT TCGA FKHR GEO ERK1/2 FTA NOS RCC Inhibitors FTC DFMO L-NMMA PD-1 ERK CRP NO OAT ABH Arginase nor‐NOHA GSK-3 SMCs PDA PDC Mechanism HSIL IFN CAFs TAMs BTLA TGF-β TIGIT NOHA CA OvCa SCLC BEC EVs CRCLM NSCLC STAT3 AKT PIC TME COX VLCs S6K1 GBex MDSCs STAT SCC TNF-α GGT TIL CTL Cancer
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Summary:	Arginase is a key hydrolase in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. Increasing number of studies in recent years demonstrate that two mammalian arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), were aberrantly upregulated in various types of cancers, and played crucial roles in the regulation of tumor growth and metastasis through various mechanisms such as regulating L-arginine metabolism, influencing tumor immune microenvironment, etc. Thus, arginase receives increasing focus as an attractive target for cancer therapy. In this review, we provide a comprehensive overview of the physiological and biological roles of arginase in a variety of cancers, and shed light on the underlying mechanisms of arginase mediating cancer cells growth and development, as well as summarize the recent clinical research advances of targeting arginase for cancer therapy. [Display omitted] •Arginase is a potential diagnostic biomarker for cancer progression.•Arginase plays a pivotal role in tumorigenesis and metastasis.•Polyamine synthesis, NO production, and immune escape are implicated in arginase-mediated cancer progression.•Arginase modulates oncogenic signaling pathways such as PI3K/AKT/mTOR, STAT3 and MAPK.•Targeting arginase by inhibitors and vaccines is a promising approach for cancer therapy.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	0753-3322 1950-6007
DOI:	10.1016/j.biopha.2022.112840