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Nature Study Flags ATF4 as Driver of Metastasis in Older Lung Cancer

Researchers call for biomarker-guided trials targeting older patients with high ATF4 activity.

Overview

  • University of Gothenburg scientists report in Nature that aging reshapes lung tumor evolution via the integrated stress response centered on ATF4.
  • Age-appropriate mouse models and records from about 1,000 patients in Halland and Västra Götaland showed smaller, slower primary tumors in older hosts yet more frequent metastatic spread.
  • Tumors from older individuals exhibited elevated ATF4, which was linked to higher recurrence after surgery and poorer survival in lung adenocarcinoma.
  • Blocking ATF4 signaling or related glutamine metabolism in aged mice significantly reduced tumor dissemination in preclinical experiments.
  • The findings position ATF4 as a potential biomarker and therapeutic target, with clinical validation and age-stratified trials proposed but not yet tested in humans.