Mitrakas Achilleas G, Kakouratos Christos, Lamprou Ioannis, Xanthopoulou Erasmia, Koukourakis Michael I
Department of Radiotherapy/Oncology, University Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Cancers (Basel). 2025 Mar 1;17(5):853. doi: 10.3390/cancers17050853.
BACKGROUND/OBJECTIVES: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related deaths globally. The study focuses on understanding the interplay between genetic mutations, cancer stem cells (CSCs), and the tumor microenvironment (TME) in driving NSCLC progression, resistance to therapies, and relapse.
A systematic search was conducted in PubMed and Scopus databases to identify significant and valuable studies relevant to NSCLC, focusing on genetic mutations, CSCs, and the TME. Articles were selected based on their relevance, methodological severity, date of publication, and scientific soundness related to NSCLC biology and therapeutic strategies. This review synthesized findings from these sources to highlight key mechanisms and potential therapeutic interventions.
Mutations in critical genes in , , , and other key genes interfere with stem cell regulation, promoting CSC-like behavior, resistance to therapy, and immune evasion. The tumor microenvironment (TME), including immune cells, fibroblasts, and extracellular matrix components, further supports tumor growth and reduction in treatment efficacy. Promising strategies, including CSC targeting, TME modulation, and the development of novel biomarkers, have shown potential in preclinical and clinical studies.
The association between genetic alterations, CSCs, the TME, and other cellular pathways-including cell metabolism and immune evasion-plays a crucial role in therapy resistance, highlighting the need for comprehensive treatment strategies. The combination of genomic profiling with TME-targeting therapies could lead to personalized treatment approaches, offering hope for better clinical outcomes and reduced mortality in NSCLC patients.
背景/目的：非小细胞肺癌（NSCLC）是全球癌症相关死亡的主要原因。该研究聚焦于了解基因突变、癌症干细胞（CSCs）和肿瘤微环境（TME）之间的相互作用在推动NSCLC进展、治疗耐药性和复发方面的作用。
在PubMed和Scopus数据库中进行了系统检索，以确定与NSCLC相关的重要且有价值的研究，重点关注基因突变、CSCs和TME。根据文章与NSCLC生物学和治疗策略的相关性、方法的严谨性、发表日期以及科学合理性来选择文章。本综述综合了这些来源的研究结果，以突出关键机制和潜在的治疗干预措施。
、 、 及其他关键基因的突变会干扰干细胞调节，促进类似CSC的行为、治疗耐药性和免疫逃逸。肿瘤微环境（TME），包括免疫细胞、成纤维细胞和细胞外基质成分，进一步支持肿瘤生长并降低治疗效果。有前景的策略，包括靶向CSC、调节TME和开发新型生物标志物，在临床前和临床研究中已显示出潜力。
基因改变、CSCs、TME与其他细胞途径（包括细胞代谢和免疫逃逸）之间的关联在治疗耐药性中起关键作用，凸显了综合治疗策略的必要性。基因组分析与靶向TME疗法的结合可能会带来个性化的治疗方法，为改善NSCLC患者的临床结局和降低死亡率带来希望。
