Arginine metabolism: a potential target in pancreatic cancer therapy

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 altere...

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Bibliographic Details
Published inChinese medical journal Vol. 134; no. 1; pp. 28 - 37
Main Authors Yang, Jin-Shou, Wang, Cheng-Cheng, Qiu, Jiang-Dong, Ren, Bo, You, Lei
Format Journal Article
LanguageEnglish
Published China Lippincott Williams & Wilkins 04.11.2020
Lippincott Williams & Wilkins Ovid Technologies
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
Wolters Kluwer
Subjects
Amino acids
Cell growth
Enzymes
Hypoxia
Immunotherapy
Kinases
Medical prognosis
Melanoma
Metabolism
Nitric oxide
Pancreatic cancer
Polyamines
Proteins
Review
Tumors
Therapy
Pancreatic cancer
Arginine metabolism
Arginine deiminase
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Summary: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.
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ISSN:0366-6999
2542-5641
2542-5641
DOI:10.1097/CM9.0000000000001216