Abstract
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second deadliest cancer by 2030, and the overall 5-year survival rate is currently less than 7%. Cancer cells frequently exhibit reprogramming of their metabolic activity. It is increasingly recognized that aberrant de novo lipid synthesis and reprogrammed lipid metabolism are both associated with the development and progression of various cancers, including pancreatic cancer. In this review, the current knowledge about lipid metabolism and lipid droplets in pancreatic cancer is discussed. In the first part, molecular mechanisms of lipid metabolism and roles of enzymes involved in lipid metabolism which are relevant for pancreatic cancer research are presented. Further, preclinical studies and clinical trials with drugs/inhibitors targeting cancer metabolic systems in cancer are summarized. An increase of our knowledge in lipid metabolism in pancreatic cancer cells and in tumor stroma is important for developing novel strategies of future individualized therapies of pancreatic cancer.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an unfavorable outcome due to late diagnosis, which is often due to a lack of sensitive and specific tumor markers despite enormous advances in our understanding of pancreatic cancer biology
We summarize several preclinical studies and clinical trials, from other cancer types which may be important for future research and therapy of pancreatic cancer
From preclinical cancer models to clinical trials, it has become apparent that lipid metabolism plays a crucial role in pancreatic cancer
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an unfavorable outcome due to late diagnosis, which is often due to a lack of sensitive and specific tumor markers despite enormous advances in our understanding of pancreatic cancer biology. Lipids can sufficiently stimulate proliferation of pancreatic cancer cells lines [6], but a wide variety of can increase oncogenic KRAS activity leading to more fibrotic stroma and enhanced PDAC tumors have activated de novo synthesis of fatty acids (FAs) irrespective of the levels of circulating development [5]. EGFR signaling is required for oncogenic KRAS-induced pancreatic tumorigenesis [16,17], and EGFR signaling activation induces upregulation of FASN in pancreatic cancer cells in an ERK-dependent manner [18] Along this line, PDAC patients with high SREBP1 expression have a shorter overall survival than patients with low SREBP1 expression, and knockdown of SREBP1 decreases pancreatic cancer cell viability and proliferation [19]. Oncogenic signaling pathways activate expression of lipogenic enzymes leading to aberrant activation of FA synthesis, which supports cancer cell development including pancreatic cancer
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