文章：

致癌突变与肿瘤微环境：非小细胞肺癌进展的双重驱动因素

Oncogenic Mutations and the Tumor Microenvironment: Drivers of Non-Small Cell Lung Cancer Progression

原文发布日期：1 March 2025

DOI: 10.3390/cancers17050853

类型: Article

开放获取: 是

英文摘要：

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. Methods: 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. Results: Mutations in critical genes inKRAS,EGFR,TP53, 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. Conclusions: 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.

摘要翻译： 

**背景/目的：** 非小细胞肺癌是全球癌症相关死亡的主要原因。本研究旨在深入理解基因突变、癌症干细胞与肿瘤微环境之间的相互作用如何驱动NSCLC的进展、治疗抵抗及复发。 **方法：** 在PubMed和Scopus数据库中进行系统性检索，以识别与NSCLC相关、重点关注基因突变、癌症干细胞和肿瘤微环境的重要且有价值的研究。文献筛选基于其与NSCLC生物学及治疗策略的相关性、方法学严谨性、发表日期及科学可靠性。本综述综合了这些来源的研究结果，以阐明关键机制和潜在的治疗干预措施。 **结果：** KRAS、EGFR、TP53等关键基因的突变干扰干细胞调控，促进癌症干细胞样行为、治疗抵抗和免疫逃逸。肿瘤微环境，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。包括靶向癌症干细胞、调节肿瘤微环境以及开发新型生物标志物在内的有前景的策略，已在临床前和临床研究中显示出潜力。 **结论：** 基因改变、癌症干细胞、肿瘤微环境以及其他细胞通路（包括细胞代谢和免疫逃逸）之间的关联在治疗抵抗中起着至关重要的作用，这凸显了采取综合治疗策略的必要性。将基因组分析与靶向肿瘤微环境的疗法相结合，可能催生个体化治疗方案，为改善NSCLC患者的临床预后和降低死亡率带来希望。

原文链接：

Oncogenic Mutations and the Tumor Microenvironment: Drivers of Non-Small Cell Lung Cancer Progression