Therapeutic targeting of lipid metabolism in cancer: Mechanisms, pathways, and translational prospects.

Cancer cells undergo intense metabolic reprogramming to provide fast proliferation, persistence, immune evasion, and resistance to therapy. Malignant cells often rely on exogenous lipids and maintaining strict metabolic regulation. Cancer cells stimulate de novo lipogenesis, lipid uptake, and storage pathways even in nutrient-limited microenvironments. This review combines current knowledge of cancer types, highlights vital enzymatic regulators and translational prospects. A comprehensive literature review was conducted, focusing on the complex relationship between lipid metabolic pathways and oncogenesis. This review focuses on de novo fatty acid synthesis, lipid uptake mechanisms, and cholesterol regulation in cancer. Important therapeutic targets, including Acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY), fatty acid synthase (FASN), and sterol regulatory element-binding proteins (SREBPs) were evaluated. It also emphasizes the role in resistance to chemotherapy, radiotherapy, and specific targeted therapies. Several studies have revealed that dysregulated lipid metabolism contributes to tumour growth, immune evasion, and treatment resistance. Evidence from preclinical and clinical studies revealed that treatments targeting small-molecule inhibitors of FASN, ACLY, SREBPs and CD36, show promising outcomes. Alterations in lipid metabolic pathways serve as critical nodes in oncogenic networks and immune modulation. The inclusion of dietetaey modifications and nanoparticle-conjugated drug delivery provides encouraging results against tumour development. This review combines the roles of key regulators, therapeutic targets, and biomarker approaches that can update future therapies. However, challenges persist, including drug-induced toxicity, metabolic changes, and tumour heterogeneity.