Lipid Dysregulation in Renal Cancer: Drivers of Tumor Growth and Determinants of Treatment-Induced Toxicity.

作者：M. Alnukhali, A. Fornoni, Alan Pollack, Anis Ahmad · 发表于：Seminars in Cancer Biology · 年份：2026 · DOI：10.1016/j.semcancer.2025.12.010 · 被引用次数：5 · 研究领域：Medicine

BACKGROUND Clear cell renal cell carcinoma (ccRCC) exhibits a distinctive metabolic signature marked by the excessive buildup of cholesterol and neutral lipids. This phenotype stems largely from the loss of the von Hippel-Lindau (VHL) tumor suppressor and the resulting stabilization of hypoxia-inducible factors (HIFs). The altered lipid environment enables ccRCC cells to sustain growth, evade immune surveillance, and withstand contemporary systemic therapies. Increasing evidence indicates that similar disturbances in lipid metabolism contribute to kidney injury during cancer treatment, suggesting that dysregulated cholesterol handling represents a shared pathologic foundation linking tumor progression with therapy-induced nephrotoxicity. SCOPE OF REVIEW This review brings together mechanistic, preclinical, and translational findings that illuminate how defective cholesterol regulation-particularly diminished ABCA1-mediated efflux promotes tumor aggressiveness while heightening renal vulnerability to radiation therapy, tyrosine kinase inhibitors (TKIs), and immune checkpoint inhibitors (ICIs). We examine lipid droplet dynamics, cholesteryl ester biology, and mitochondrial perturbations in ccRCC cells and renal parenchymal cells exposed to therapeutic stress. MAJOR CONCLUSIONS Across ccRCC therapies, lipid accumulation drives renal injury, with lipid-sensitive cells, particularly podocytes, undergoing cytoskeletal and slit-diaphragm disruption, proteinuria, and progressive ...