Fatty acids in cancer: Metabolic functions and potential treatment

Abstract

Lipid metabolic reprogramming is one of the important metabolic characteristics of cancer cells. As major components of lipids, fatty acids provide energy and material basis for cancer cell survival. Abnormal fatty acid metabolism has been found in many cancers. Fatty acid uptake, transport, and synthesis are closely related to the pathogenesis of cancer. Meanwhile, fatty acid changes in the membrane structure of cancer cells and signal transduction mediated by signaling lipids are also helping cancer cells survive in the changing microenvironment. Some of these enzymes and metabolites involved in fatty acid metabolism are emerging as unique cancer biomarkers. Multiple studies have shown that disordered fatty acids can regulate tumor cell proliferation, metastasis, and drug resistance. Therefore, targeting fatty acid metabolism has become a promising treatment strategy. Here, we mainly present metabolic alterations of fatty acids, the basic components of lipids, in cancer. We discuss the cancer treatment based on fatty acid and fatty acid metabolism. These may provide a basis for a better understanding of lipid metabolic reprogramming in cancer, and also provide new ideas for cancer biomarker search, drug development, and combination therapy.

Metabolomics at the tumor microenvironment interface: Decoding cellular conversations

“…44 As well, alterations of FA metabolism contribute to cellular proliferation, epithelial-mesenchymal transition, migration, and invasion. 45 The de novo synthesis of saturated polysaccharides that contribute to cell membrane structure in tumorigenesis also allows for cells to become more resistant to oxidative stress caused by chemotherapy. 44 Cholesterol has been considered a high-risk factor and prognostic indicator.…”

“…107 Other studies have also identified increased lipids in the cell membranes to be associated with radiotherapy and chemotherapy resistance. 45 Furthermore, blocking de novo FA synthesis may increase cancer cell sensitivity. 45 Targeting FA synthesis as an anticancer therapeutic has been speculated to be promising, however, the translation of this clinic has been Abbreviations: ADI-PEG, pegylated arginine deiminase; CTLA4, cytotoxic T-lymphocyte-associated protein 4; IGF1, insulin-like growth factor-1; MDSC, myeloid-derived suppressor cell; NSCLC, non-small cell lung cancer; pCR, pathologic complete response; PD-1/PD-L1, programmed cell death protein 1/programmed cell death ligand 1; TIL, tumor infiltrating lymphocyte; TME, tumor microenvironment.…”

“…FAs are essential to rapid proliferation as they are essential in membrane biosynthesis and provide nutrients and energy in metabolic stress 44 . As well, alterations of FA metabolism contribute to cellular proliferation, epithelial–mesenchymal transition, migration, and invasion 45 . The de novo synthesis of saturated polysaccharides that contribute to cell membrane structure in tumorigenesis also allows for cells to become more resistant to oxidative stress caused by chemotherapy 44 .…”

“…Enhanced FA oxidation has been found to be used in limited glucose conditions which additionally, through ROS generation, provides resistance to oxidative stress and activates protumour survival pathways 107 . Other studies have also identified increased lipids in the cell membranes to be associated with radiotherapy and chemotherapy resistance 45 . Furthermore, blocking de novo FA synthesis may increase cancer cell sensitivity 45 .…”

“…Other studies have also identified increased lipids in the cell membranes to be associated with radiotherapy and chemotherapy resistance 45 . Furthermore, blocking de novo FA synthesis may increase cancer cell sensitivity 45 . Targeting FA synthesis as an anticancer therapeutic has been speculated to be promising, however, the translation of this clinic has been problematic due to severe side effects 44 .…”