Potential Roles of Tumor Microenvironment in Gefitinib-Resistant Non-Small Cell Lung Cancer: A Narrative Review

During the course of treating non-small cell lung cancer (NSCLC) with epithelial growth factor receptor (EGFR) mutant, gefitinib resistance (GR) is unavoidable. As the environment for tumor cells to grow and survive, tumor microenvironment (TME) can significantly affect therapeutic response and clinical outcomes, offering new opportunities for addressing GR. Dynamic changes within the TME were identified during the treatment of gefitinib, suggesting the close relationship between TME and GR. Various dynamic processes like angiogenesis, hypoxia-pathway activation, and immune evasion can be blocked so as to synergistically enhance the therapeutic effects of gefitinib or reverse GR. Besides, cellular components like macrophages can be reprogrammed for the same purpose. In this review, we summarized recently proposed therapeutic targets to provide an overview of the potential roles of TME in treating gefitinib-resistant NSCLC, and discussed the difficulty of applying these targets in cancer treatment.