Abstract

Lipid droplets (LDs) play crucial roles in cellular metabolism and stress responses, particularly in cancer cells,contributing significantly to survival, growth, and therapeutic resistance. This review explores the multifaceted involvement of LDs in cancer biology, focusing on their biogenesis, molecular regulation, and impact on cellular metabolism under stress conditions. LDs are dynamic organelles that store and mobilize lipids, essential for energy homeostasis and membrane synthesis in rapidly proliferating cancer cells. Mechanistically, LD formation is regulated by signaling pathways such as mTOR and AMPK, which integrate metabolic cues and stress signals to modulate lipid metabolism. Interactions between LDs and other organelles, including mitochondria and the endoplasmic reticulum, further influence cellular metabolism and stress responses in cancer. Importantly, LD-mediated stress adaptations enable cancer cells to survive hostile tumor microenvironments characterized by oxidative stress, hypoxia, and nutrient deprivation. These adaptations contribute to therapeutic resistance and disease progression, highlighting LDs as potential targets for novel cancer therapies. Future research should focus on elucidating specific molecular mechanisms governing LD dynamics in cancer, exploring their heterogeneity within tumors, and leveraging interdisciplinary approaches to translate findings into clinical applications.