Reprogramming of Lipid Metabolism in Cancer Cells

Metabolic reprogramming is a defining hallmark of cancer, and dysregulated lipid metabolism has emerged as a third major axis of this reprogramming alongside the Warburg effect and glutamine addiction. Cancer cells enhance de novo lipogenesis, increase exogenous lipid uptake, rewire fatty acid oxidation, dysregulate cholesterol handling, and accumulate lipid droplets to support membrane biogenesis, energy production, and oncogenic signaling. These pathways are coordinated by master regulators—SREBPs, PPARs, and the mTOR/AMPK axis—that integrate oncogenic and microenvironmental cues. Lipid reprogramming also shapes the tumor microenvironment by modulating stromal and immune cell metabolism, contributing to immune evasion, epithelial-to-mesenchymal transition, metastasis, and resistance to chemotherapy and immunotherapy. Given its central role across malignancy, lipid metabolism has become an attractive therapeutic target, with inhibitors of lipogenic enzymes, fatty acid oxidation, and cholesterol synthesis now under preclinical and clinical investigation, including in combination with immune checkpoint blockade. This review summarizes the major pathways and regulatory mechanisms underlying lipid metabolic reprogramming in cancer cells, its contribution to tumor progression, and current therapeutic strategies targeting these metabolic vulnerabilities

کلیدواژه ها:

Lipid metabolism ، Cancer ، Metabolic reprogramming ، Fatty acid oxidation ، Cholesterol ، Tumor microenvironment