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December 9, 2025Cancer Research

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

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Authors

MBMorgan R. BradyNMNedas MatulionisHCHeather R. Christofk

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Overview

This study reveals tumor growth is influenced by metabolic pathways in lung squamous cell carcinoma, suggesting new therapeutic strategies.

Key Points

  • The research aims to explore resistance mechanisms to mTOR inhibitors in lung squamous cell carcinoma.
  • Investigated effects of mTOR inhibitor TAK228 across lung squamous cell carcinoma models including cell lines and PDXs.
  • Examined the roles of macropinocytosis and angiogenesis in nutrient supply during treatment.
  • Utilized co-inhibition techniques with small molecule inhibitors for mTOR and macropinocytosis.
  • Inhibition of both mTOR and macropinocytosis reduced tumor growth in models.
  • Angiogenesis limited efficacy of treatments by maintaining nutrient supply.
  • Prolonged TAK228 and CB-839 treatment led to increased vascularization and rebound tumor growth.

Cite This Study

Brady et al. (2025) studied this question.

synapsesocial.com/papers/69401d732d562116f28f94bbhttps://doi.org/10.1158/0008-5472.can-25-0921
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract 394: Adaptive resistance mechanisms to mTOR inhibitor in lung squamous cell carcinoma.2026
  2. 2Abstract 5555: Lung squamous cancer cell mTORC2 signaling suppresses antitumor immunity by up-regulation of PSGL-1, a ligand of VISTA/PD-1H checkpoint receptor2024
  3. 3Abstract 3261: Improving targeted therapy in female patients with lung squamous cell carcinoma2024
  4. 4Abstract 4915: Using functional CRISPR screening to investigate metabolic genes in lung squamous cell carcinoma adoptive T cell therapy2026
  5. 5Harnessing lipid metabolism modulation for improved immunotherapy outcomes in lung adenocarcinoma2024 · 66 citations