Lipid droplets in cancer: A review of their implications for tumor biology and treatment

Abstract

Lipid droplets (LDs) are intracellular organelles traditionally known for their role in lipid storage and energy homeostasis. Recent research has unveiled their significant involvement in cancer biology, revealing them as dynamic structures that contribute to various aspects of tumor development and progression. This review delves into the multifaceted roles of LDs in cancer, highlighting their implications for tumor biology and potential therapeutic strategies. LDs are increasingly recognised for their ability to modulate cellular metabolism, signaling pathways, and stress responses in cancer cells. Their accumulation is often observed in various tumor types, correlating with aggressive phenotypes and poor prognosis. LDs support rapid cell proliferation by providing essential lipids for membrane synthesis and energy production, enabling cancer cells to thrive under metabolic stress. Furthermore, LDs serve as hubs for lipid signaling molecules, influencing key oncogenic pathways such as the PI3K/Akt/mTOR and Wnt/β-catenin pathways, thereby promoting tumorigenesis and metastasis. Beyond their metabolic functions, LDs contribute to the oxidative stress response and lipid peroxidation, mechanisms that can either facilitate cancer cell survival or lead to cell death, depending on the context. The dual role of LDs in regulating reactive oxygen species (ROS) levels underscores their complexity in cancer biology. Importantly, LDs have emerged as potential targets for cancer therapy. Strategies to disrupt LD formation, enhance lipid catabolism, or modulate lipid signaling are being explored to impair tumor growth and sensitize cancer cells to treatment. Pharmacological agents targeting LD-associated proteins, such as perilipins and diacylglycerol acyltransferase (DGAT) inhibitors, are showing promise in preclinical models. LDs play a critical and versatile role in cancer biology, influencing tumor metabolism, signaling, and stress responses. Understanding the intricate functions of LDs in cancer can pave the way for novel therapeutic approaches, offering hope for more effective treatments in oncology. This review underscores the need for further research to fully elucidate the therapeutic potential of targeting LDs in cancer.