Arginine metabolism: a potential target in pancreatic cancer therapy.
10.1097/CM9.0000000000001216
- Author:
Jin-Shou YANG
1
;
Cheng-Cheng WANG
;
Jiang-Dong QIU
;
Bo REN
;
Lei YOU
Author Information
1. Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.
- Publication Type:Journal Article
- MeSH:
Arginine/metabolism*;
Argininosuccinate Synthase;
Carcinoma, Pancreatic Ductal/drug therapy*;
Cell Line, Tumor;
Humans;
Pancreatic Neoplasms/drug therapy*
- From:
Chinese Medical Journal
2020;134(1):28-37
- CountryChina
- Language:English
-
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant disease, which has an extremely low survival rate of <9% in the United States. As a new hallmark of cancer, metabolism reprogramming exerts crucial impacts on PDAC development and progression. Notably, arginine metabolism is altered in PDAC cells and participates in vital signaling pathways. In addition, arginine and its metabolites including polyamine, creatine, agmatine, and nitric oxide regulate the proliferation, growth, autophagy, apoptosis, and metastasis of cancer cells. Due to the loss of argininosuccinate synthetase 1 (ASS1) expression, the key enzyme in arginine biosynthesis, arginine deprivation is regarded as a potential strategy for PDAC therapy. However, drug resistance develops during arginine depletion treatment, along with the re-expression of ASS1, metabolic dysfunction, and the appearance of anti-drug antibody. Additionally, arginase 1 exerts crucial roles in myeloid-derived suppressor cells, indicating its potential targeting by cancer immunotherapy. In this review, we introduce arginine metabolism and its impacts on PDAC cells. Also, we discuss the role of arginine metabolism in arginine deprivation therapy and immunotherapy for cancer.
