Quantitative Modeling of Lipid Droplet Contribution to Intracellular Drug Distribution and Efficacy of Tyrosine Kinase Inhibitors

values, such as sunitinib, preferentially accumulate in lysosomes, consistent with model predictions and experimental imaging results. Cytotoxicity assays confirmed the predicted bidirectional effects of LD expansion and depletion on drug efficacy. These findings identify LDs as active modulators of subcellular drug PK and suggest that targeting LD dynamics may enhance the therapeutic performance of lipophilic TKIs, especially in cancers with dysregulated lipid metabolism.