The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review)
Li Liu, Yang Li, Hongmin Li, Tianlu Shang, Li‐Han Liu
Abstract
Lung cancer remains a leading cause of cancer-related death.Despite advances in targeted therapies and immunotherapy, treatment outcomes remain suboptimal due to tumor heterogeneity and therapeutic resistance.The tumor microenvironment (TME), a dynamic ecosystem comprising immune cells, stromal components, extracellular matrix and bioactive molecules, serves a critical role in promoting tumor progression and resistance.The present review comprehensively analyzes the molecular mechanisms underlying TME-mediated immune evasion, and resistance to chemotherapy, radiotherapy and immunotherapy.In addition, emerging therapeutic strategies targeting the TME are highlighted, such as immune microenvironment modulation, metabolic and epigenetic interventions, and nanotechnology-based drug delivery systems.By integrating multi-omics datasets and spatial transcriptomics, TME-directed interventions are moving toward biomarker-guided, personalized regimens.Contents 1. Introduction 2. Heterogeneity of the lung cancer microenvironment 3. Dynamic crosstalk in the TME: Mechanisms of progression 4. TME-driven therapeutic resistance in lung cancer 5. Challenges and future directions 6. Therapeutic strategies and clinical application of the TME 7. Conclusion