Macropinocytosis and Vascularization Determine Response to mTOR Inhibitors in Lung Squamous Cell Carcinoma.

ABSTRACT: The capacity of cancer cells to rewire their cellular metabolism in response to therapeutic pressure confers resistance to treatments targeting key metabolic pathways, which represents a significant challenge in personalized cancer therapy for lung tumors. In this study, we investigated the mechanisms of resistance to the small molecule mTOR inhibitor TAK228 across lung squamous cell carcinoma (LUSC) models, including cell lines, xenografts, and patient-derived xenografts (PDXs). LUSC cells adapted to mTOR inhibition by engaging macropinocytosis, a form of endocytosis that facilitates enhanced uptake of extracellular nutrients, thereby increasing amino acid availability. Co-inhibition of both mTOR and macropinocytosis using small molecule inhibitors effectively reduced tumor growth. Additi

SUBMITTER: Brady MR 

PROVIDER: S-EPMC12774322 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature