Lipid Metabolism in Oncology: Why It Matters, How to Research, and How to Treat

Abstract

Lipids in our body, which are mainly composed of fatty acids, triacylglycerides, sphingolipids, phospholipids, and cholesterol, play important roles at the cellular level. In addition to being energy sources and structural components of biological membranes, several types of lipids serve as signaling molecules or secondary messengers. Metabolic reprogramming has been recognized as a hallmark of cancer, but changes in lipid metabolism in cancer have received less attention compared to glucose or glutamine metabolism. However, recent innovations in mass spectrometry- and chromatography-based lipidomics technologies have increased our understanding of the role of lipids in cancer. Changes in lipid metabolism, so-called “lipid metabolic reprogramming”, can affect cellular functions including the cell cycle, proliferation, growth, and differentiation, leading to carcinogenesis. Moreover, interactions between cancer cells and adjacent immune cells through altered lipid metabolism are known to support tumor growth and progression. Characterization of cancer-specific lipid metabolism can be used to identify novel metabolic targets for cancer treatment, and indeed, several clinical trials are currently underway. Thus, we discuss the latest findings on the roles of lipid metabolism in cancer biology and introduce current advances in lipidomics technologies, focusing on their applications in cancer research.

Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

“…Therefore, blocking glucose and glutamine metabolism in HDAC5-knock down cancer cells significantly induced cell death, which provided insight into a combination therapy with HDAC5 inhibitors and various inhibitors of metabolism as a new strategy for cancer treatment. During tumorigenesis, cancer cells often undergone deregulated lipid metabolism (134). Statins, a class of 3hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, can modulate the cell cycle, signal transduction pathways, and angiogenesis, and thus have therapeutic potential in cancer treatment (135)(136)(137)(138)(139).…”

Flexibility of a mammalian lipidome — insights from mouse lipidomics

“…Lipidomics has successfully been applied to study disease and disease-related mechanisms in many different indications. Among these are neurological disorders [Bosch-Queralt et al, 2021, Cascalho et al, 2020, liver disease [Parker et al, 2019] and cancer [Bi et al, 2019, Peck et al, 2016, Saliakoura et al, 2020, resulting in the identification of potential drug targets involved in lipid metabolism [Matsushita et al, 2021]. A primary model for these studies is the mouse Mus musculus.…”

Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy

“…Lipids are essential nutrients for cells, acting as the structural components of cell membranes, signaling molecules and energy suppliers. Lipids can be classified into several groups, but the most abundant lipids are fatty acids, triglycerides, sphingolipids, phospholipids and cholesterol [74]. Abundant lipids were detected in aggressive CRC, in line with the fact that CRC was accompanied by upregulated lipogenesis [75][76][77][78][79][80].…”

“…When the fatty acids are partitioned into the FAO (fatty acid oxidation pathway), they must translocate across the mitochondrial membrane [74]. Carnitine palmitoyltransferase 1 (CPT1) is responsible for the conversion of acyl-CoA into acyl carnitine by coupling to carnitine.…”

“…The translocation of acyl carnitine is mediated by carnitine acyl carnitine translocase (CACT). Once delivered into mitochondria, acyl carnitine is returned to the acyl-CoA by carnitine palmitoyltransferase 2 (CPT2) [74]. In FAO, acyl-CoA is processed further, and the end product, acetyl-CoA, is then involved in the TCA cycle [74].…”