Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.
Chin Med J (Engl). 2020 Nov 4;134(1):28-37. doi: 10.1097/CM9.0000000000001216.
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.
胰腺导管腺癌 (PDAC) 是一种极其恶性的疾病，在美国的生存率极低，<9%。作为癌症的一个新标志，代谢重编程对 PDAC 的发展和进展产生了至关重要的影响。值得注意的是，精氨酸代谢在 PDAC 细胞中发生改变，并参与重要的信号通路。此外，精氨酸及其代谢物，包括多胺、肌酸、胍丁胺和一氧化氮，调节癌细胞的增殖、生长、自噬、凋亡和转移。由于精氨酸生物合成的关键酶精氨酸合成酶 1 (ASS1) 的表达缺失，精氨酸剥夺被认为是 PDAC 治疗的一种潜在策略。然而，在精氨酸耗竭治疗过程中会产生耐药性，同时 ASS1 的重新表达、代谢功能障碍和抗药性抗体的出现。此外，精氨酸酶 1 在髓源性抑制细胞中发挥着重要作用，表明其可能成为癌症免疫治疗的靶点。在这篇综述中，我们介绍了精氨酸代谢及其对 PDAC 细胞的影响。还讨论了精氨酸代谢在精氨酸剥夺治疗和癌症免疫治疗中的作用。
