Patient-derived organoids: Advancing research on bioactive natural compounds in lung cancer

Abstract

Lung cancer, the leading cause of cancer-related deaths, demands innovative models for therapy development. Bioactive natural compounds, with their structural diversity and historical therapeutic significance, remain pivotal in drug discovery for combating lung malignancies. Patient-derived organoids (PDOs) surpass conventional models by preserving tumor heterogeneity, molecular profiles, and tumor microenvironment (TME) dynamics, enabling accurate drug response prediction and personalized therapy design. Recent studies leveraging lung cancer PDOs have validated several plant-derived agents for their tumor-suppressive effects, potential for chemosensitivity enhancement, and subtype-specific efficacy. Advanced co-culture systems incorporating TME components have improved preclinical-to-clinical translatability. The technological integration of bioengineered platforms (e.g., microfluidic systems, 3D bioprinting) and artificial intelligence has further enhanced high-throughput screening and clinical correlation of drug responses. Although lung cancer PDOs exhibit inherent limitations, these advancements establish PDOs as important tools for evaluating the efficacy-toxicity profiles of bioactive natural compounds and advancing precision oncology in lung cancer.