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The role of cholesterol metabolism reprogramming in pancreatic cancer and the application of cholesterol-targeted metabolism drugs

ZHAO Rui-Li^1,2, LI Qian-Qian^1,2, LIU Yue-Se^1,2, ZHANG Juan^3,1,2,*

¹The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450046, China；²Department of Oncology, Henan Provincial Hospital of Traditional Chinese Medicine (The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou 450002, China；³The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China

Abstract

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.

Key words: pancreatic cancer; cholesterol; lipid metabolism; metabolic reprogramming

Received: 　　Accepted:

Corresponding author: 张娟　　E-mail: cancer126@126.com

Citing This Article：

ZHAO Rui-Li, LI Qian-Qian, LIU Yue-Se, ZHANG Juan. The role of cholesterol metabolism reprogramming in pancreatic cancer and the application of cholesterol-targeted metabolism drugs. Acta Physiol Sin 2023; 75 (3): 413-428 (in Chinese with English abstract).