Bridging the gap: how patient-derived lung cancer organoids are transforming personalized medicine

Lung cancer is a major malignancy that poses a significant threat to human health, with its complex pathogenesis and molecular characteristics presenting substantial challenges for treatment. Traditional two-dimensional cell cultures and animal models are limited in their ability to accurately replicate the characteristics of different lung cancer patients, thereby hindering research on disease mechanisms and treatment strategies. The development of organoid technology has enabled the growth of patient-derived tumor cells in three-dimensional cultures, which can stably preserve the tumor's tissue morphology, genomic features, and drug response. There have been significant advancements in the field of patient-derived lung cancer organoids (PDLCOs), challenges remain in the reproducibility and standardization of PDLCOs models due to variations in specimen sources, subsequent processing techniques, culture medium formulations, and Matrigel batches. This review summarizes the cultivation and validation processes of PDLCOs and explores their clinical applications in personalized treatment, drug screening after resistance, PDLCOs biobanks construction, and drug development. Additionally, the integration of PDLCOs with cutting-edge technologies in various fields, such as tumor assembloid techniques, artificial intelligence, organoid-on-a-chip, 3D bioprinting, gene editing, and single-cell RNA sequencing, has greatly expanded their clinical potential. This review, incorporating the latest research developments in PDLCOs, provides an overview of their cultivation, clinical applications, and interdisciplinary integration, while also addressing the prospects and challenges of PDLCOs in precision medicine for lung cancer.