Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer

Abstract

There is growing evidence that metabolic alterations play an important role in cancer development and progression. The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation. Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism. An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival, as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival. Based on the data that serum fatty acid synthase (FASN), also known as oncoantigen 519, is elevated in patients with certain types of cancer, its serum level was proposed as a marker of neoplasia. This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic neoplasm, characterized by high mortality. We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism. Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer. In particular, FASN is a viable candidate for indicator of pathologic state, marker of neoplasia, as well as, pharmacological treatment target in pancreatic cancer. Recent research showed that, in addition to lipogenesis, certain cancer cells can use fatty acids from circulation, derived from diet (chylomicrons), synthesized in liver, or released from adipose tissue for their growth. Thus, the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.

Statins and pancreatic cancer

“…IL, interleukin; GM-CSF, granulocyte macrophage colony-stimulating factor; VEGF, vascular endothelial growth factor; VCAM1, vascular cell adhesion molecule 1; SEH, soluble epoxide hydrolase; CYP51A1, cytochrome P450 family 51 subfamily A member 1; Acetyl-CoA, acetyl-coenzyme A; HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A; FPP, farnesyl pyrophosphate; GPP, geranyl pyrophosphate. and its components, including diabetes, obesity and dyslipidemia, have been recognized as modifiable risk factors for pancreatic cancer (72,73). Evidence discussed in the present review has demonstrated that statins potentially reduce pancreatic cancer risk and improve survival in patients with a combination of metabolic syndrome and pancreatic cancer.…”

Hyper-Elongation in Colorectal Cancer Tissue – Cerotic Acid is a Potential Novel Serum Metabolic Marker of Colorectal Malignancies

“…Carcinogenesis is associated with substantial changes in cellular metabolism, including alterations of lipid, carbohydrate, nucleic acid and amino acid metabolism [6]. These changes promote rapid proliferation of cancer cells.…”

Pancreatic cancer from bench to bedside: molecular pathways and treatment options

“…Recent studies have enlighten several metabolic routes and signaling pathways that control tumor progression (36). The most important pathways are considered the following: glutamine regulatory enzymes, Ras signaling, lipid metabolism and autophagy (37)(38)(39). Pancreatic cancer as most cancer types are characterized by a high increase in glucose uptake and metabolism (40) and high glycolytic rates the so called "Warburg effect".…”

“…Until now there was an increasing interest in glucose metabolism and aerobic glycolysis, however; it is becoming clearly evident that the alteration of lipid metabolism is critical for cancer cell metabolism (55). Enzymes involved in lipogenesis and lipolysis have been found overexpressed in pancreatic cancer, in particular fatty acid synthase (FASN) that catalyses the final steps of fatty acid synthesis and ATP citrate lyase (39). It has been observed that elevated levels of FASN protein in cancer cells and in serum of pancreatic cancer patients are associated with poor prognosis (39).…”

“…Enzymes involved in lipogenesis and lipolysis have been found overexpressed in pancreatic cancer, in particular fatty acid synthase (FASN) that catalyses the final steps of fatty acid synthesis and ATP citrate lyase (39). It has been observed that elevated levels of FASN protein in cancer cells and in serum of pancreatic cancer patients are associated with poor prognosis (39). In cancer cells hyper activation of lipogenesis is observed and characterized by an increase in the degree of lipid saturation compared with nonlipogenic tumors (56).…”