The treatment of non-small cell lung cancer (NSCLC), a disease known for its aggressiveness and significant global impact, has substantially improved in recent decades. A notable shift from cytotoxic chemotherapy to more personalized approaches, such as targeted therapies and immunotherapies, has led to improved outcomes for some patients. However, the emergence of resistance remains a major challenge in clinical practice, highlighting the inherent adaptability of cancer cells. This adaptability extends beyond genetic and epigenetic changes within malignant cells, as the bidirectional crosstalk with the tumor microenvironment (TME) also plays a crucial role. This complex ecosystem, consisting of various cellular components (e.g., fibroblasts, endothelial cells, immune cells), extracellular matrix elements, and soluble factors, significantly influences tumor progression, metastasis, and treatment response. Therefore, a comprehensive understanding of how the TME evolves under the selective pressures of different therapies is essential for developing more durable and effective treatment strategies for NSCLC.
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