Ji Hongzhi, Zhang Li, Ye Lingyun
Department of Respiratory, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China.
Department of Gastroenterology, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, China.
Front Oncol. 2025 May 15;15:1539047. doi: 10.3389/fonc.2025.1539047. eCollection 2025.
Recent studies have promoted new insights into the biology of non-small cell lung cancer (NSCLC) and made considerable progress in the field of treatment, including targeted therapy for driver gene mutations. Immunotherapy (IO) is another breakthrough, which has achieved amazing clinical efficacy. However, the survival status of advanced NSCLC patients is still unsatisfactory. Drug resistance is an urgent problem to be solved in almost all anti-cancer treatment schemes. Nowadays, platinum based chemotherapy remains the standard treatment for patients with driver gene negative advanced NSCLC. Previous studies have shown that the reduction of intracellular accumulation of platinum drugs, DNA damage repair and the enhancement of detoxification effect all lead to platinum resistance. The mechanisms of tyrosine kinase inhibitors (TKIs) resistance include the emergence of secondary mutation, the activation of bypass signal pathways, the abnormality of downstream signal pathways and the transformation of phenotype. The mechanisms of immune checkpoint inhibitors (ICIs) resistance are more complex. A variety of cells, cytokines and metabolites participate in it to form an immunosuppressive microenvironment, resulting in the impairment of effector T cell function. Exosomes are small molecules secreted by a variety of cells. They can carry information such as miRNA, lncRNA, and protein, and play a pivotal role in signal transduction between cells. More and more studies show that exosomes are important transmitters in lung cancer cells, which can transfer drug resistance information from drug-resistant cells to sensitive cells. However, the underling specific mechanisms need to be further explored to find a new breakthrough for overcoming drug resistance of NSCLC.
最近的研究对非小细胞肺癌(NSCLC)的生物学特性有了新的认识,并在治疗领域取得了显著进展,包括针对驱动基因突变的靶向治疗。免疫疗法(IO)是另一项突破,已取得了惊人的临床疗效。然而,晚期NSCLC患者的生存状况仍不尽人意。耐药性是几乎所有抗癌治疗方案中亟待解决的问题。目前,铂类化疗仍然是驱动基因阴性的晚期NSCLC患者的标准治疗方法。先前的研究表明,铂类药物细胞内蓄积减少、DNA损伤修复以及解毒作用增强均会导致铂耐药。酪氨酸激酶抑制剂(TKIs)耐药的机制包括二次突变的出现、旁路信号通路的激活、下游信号通路的异常以及表型转化。免疫检查点抑制剂(ICIs)耐药的机制更为复杂。多种细胞、细胞因子和代谢产物参与其中,形成免疫抑制微环境,导致效应T细胞功能受损。外泌体是多种细胞分泌的小分子。它们可以携带miRNA、lncRNA和蛋白质等信息,并在细胞间信号转导中起关键作用。越来越多的研究表明,外泌体是肺癌细胞中的重要传递者,能够将耐药信息从耐药细胞传递到敏感细胞。然而,其具体机制仍需进一步探索,以便为克服NSCLC的耐药性找到新的突破点。