Organoid-based precision cancer modeling: New frontier in lung cancer research

Cell Rep. 2025 Dec 23;44(12):116595. doi: 10.1016/j.celrep.2025.116595. Epub 2025 Nov 20.

Abstract

Lung cancer remains a leading cause of cancer-related mortality globally, underscoring the need for advanced preclinical models that accurately recapitulate disease biology. Recent advances in organoid technology have enabled the establishment of patient-derived lung cancer organoids (LCOs), which faithfully reproduce the histological, genetic, and phenotypic features of primary tumors. This organoid-based precision modeling facilitates deeper insights into tumor biology and disease progression, supporting the identification of novel therapeutic targets and biomarkers. In this review, we summarize recent progress in LCO-based precision modeling, focusing on their ability to preserve tumor heterogeneity, link genotype and phenotype through multi-omics integration, and explore tumor-microenvironment interactions via gene editing and co-culture systems. We also highlight the growing importance of LCO biobanks and international collaborations in translational research. Despite challenges such as low establishment efficiency, LCO-based precision modeling offers a powerful platform for understanding lung cancer pathogenesis and guiding the development of more effective therapies.

Keywords: CP: cancer; lung cancer; organoid library; patient-derived organoid; personalized therapy; precision medicine; review.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Models, Biological*
  • Organoids* / metabolism
  • Organoids* / pathology
  • Precision Medicine* / methods
  • Tumor Microenvironment