Targeting lipid biosynthesis on the basis of conventional treatments for clear cell renal cell carcinoma: A promising therapeutic approach

A variety of cancer cells exhibit dysregulated lipid metabolism, characterized by excessive intracellular lipid accumulation, and clear cell renal cell carcinoma (ccRCC) is the most typical disease with these characteristics. As the most common malignancy of all renal cell carcinomas (RCCs), ccRCC is typically characterized by a large accumulation of lipids and glycogen in the cytoplasm and a nucleus that is squeezed by the accumulated lipid droplets and localized to the marginal areas within the cytoplasm. This lipid accumulation has been found to be critically involved in the maintenance of malignant features observed in various cancers. Firstly, it maintains the persistent proliferative and metastasis properties of cancer cells. Secondly, it acts as a buffer against lipid peroxidation, preventing lipid peroxidation-induced ferroptosis. Moreover, lipids can diminish the sensitivity of cancer cells to radiotherapy. As ccRCC is a type of cancer with high lipid synthesis, targeting lipid synthesis-related genes in cancer cells may be a promising therapeutic modality for single treatment or in combination with radiotherapy, chemotherapy, and immunotherapy. This may revolutionize the choice of treatment modality for ccRCC patients. In this review, we concentrate on the current status and progress of research on lipid biosynthesis in ccRCC and the potential applications of targeting lipid synthesis to treat ccRCC. At last, we propose perspective and future research directions for targeting inhibition of lipid biosynthesis in combination with conventional therapeutic approaches for the treatment of ccRCC, which will help to evolve the therapeutic model.