Harnessing Nanotechnology to Rewire Lipid Metabolism: A Novel Therapeutic Avenue for Brain Cancer

The uncontrolled proliferation of abnormal brain cells characterizes brain cancer. It is lethal and develops resistance upon treatment with commonly available modalities, such as chemotherapy and radiotherapy. Findings showed that the altered metabolic programming in brain cancer is one of the major hallmarks that supports the energy expenditures of the malignant cells. As evidenced, brain tumors showed elevated de novo lipid synthesis to support membrane biosynthesis, activation of oncogenic signaling, and energy storage. The most common enzymes required for lipid biosynthesis include fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding proteins (SREBPs), which are found to be upregulated during brain cancer progression. Importantly, altered lipid metabolism not only fuels tumor growth but also modulates the tumor microenvironment (TME), restricting the infiltration of immune cells, inactivating the immune cells, and ultimately promoting the development of therapeutic resistance. Therefore, unraveling how lipid biosynthesis fuels brain cancer progression is of greater importance than ever so that it could unlock new avenues for developing precise and effective targeted therapies. In the past few years, the use of nanotechnology-based delivery systems has shown promising results in selective targeting of lipid metabolic pathways while minimizing secondary toxicities, paving the way for more effective and personalized treatment approaches. This review explains how lipid biosynthesis drives brain cancer progression and the potential of a nanotechnology-based approach to modulate the abnormal lipid metabolism in brain cancer.