Zhao Rui-Li, Li Qian-Qian, Liu Yue-Se, Zhang Juan
The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China.
Department of Oncology, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou 450002, China.
Sheng Li Xue Bao. 2023 Jun 25;75(3):413-428.
Pancreatic cancer has an insidious onset and lacks effective treatment methods, which is one of the tumors with the worst prognosis, so it is urgent to explore new treatment directions. Metabolic reprogramming is one of the important hallmarks of tumors. Pancreatic cancer cells in the harsh tumor microenvironment have comprehensively increased cholesterol metabolism in order to maintain strong metabolic needs, and cancer associated fibroblasts also provide cancer cells with a large amount of lipids. Cholesterol metabolism reprogramming involves the changes in the synthesis, uptake, esterification and metabolites of cholesterol, which are closely related to the proliferation, invasion, metastasis, drug resistance, and immunosuppression of pancreatic cancer. Inhibition of cholesterol metabolism has obvious anti-tumor effect. In this paper, the important effects and complexity of cholesterol metabolism in pancreatic cancer were comprehensively reviewed from perspectives of risk factors for pancreatic cancer, energy interaction between tumor-related cells, key targets of cholesterol metabolism and its targeted drugs. Cholesterol metabolism has a strict regulation and feedback mechanism, and the effect of single-target drugs in clinical application is not clear. Therefore, multi-target therapy of cholesterol metabolism is a new direction for pancreatic cancer treatment.
胰腺癌起病隐匿,缺乏有效的治疗方法,是预后最差的肿瘤之一,因此亟待探索新的治疗方向。代谢重编程是肿瘤的重要特征之一。处于恶劣肿瘤微环境中的胰腺癌细胞为维持旺盛的代谢需求,全面增强了胆固醇代谢,且癌症相关成纤维细胞也为癌细胞提供大量脂质。胆固醇代谢重编程涉及胆固醇合成、摄取、酯化及代谢产物的变化,这与胰腺癌的增殖、侵袭、转移、耐药及免疫抑制密切相关。抑制胆固醇代谢具有明显的抗肿瘤作用。本文从胰腺癌的危险因素、肿瘤相关细胞间的能量相互作用、胆固醇代谢关键靶点及其靶向药物等方面,全面综述了胆固醇代谢在胰腺癌中的重要作用及复杂性。胆固醇代谢具有严格的调控和反馈机制,单靶点药物在临床应用中的效果尚不明确。因此,胆固醇代谢的多靶点治疗是胰腺癌治疗的新方向。