The tumor microenvironment in lung cancer: Heterogeneity, therapeutic resistance and emerging treatment strategies (Review)

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.