文章：

EGFR突变型肺癌中的细胞死亡、分子靶向治疗与代谢重编程

Cell Death, Molecular Targeted Therapies, and Metabolic Reprogramming in EGFR-Mutant Lung Cancer

原文发布日期：27 August 2025

DOI: 10.3390/cancers17172791

类型: Article

开放获取: 是

英文摘要：

Lung cancer is responsible for high morbidity and mortality worldwide. In general, lung cancer can be divided into two major types, including small cell lung carcinoma (SCLC) and the more common non-small cell lung carcinoma (NSCLC). Molecular events underlying lung cancer development, growth, and progression remain complex. In addition to a variety of genetic aberrations, alterations in cellular metabolism have been implicated. Epidermal growth factor receptor (EGFR) is a cell surface protein that is frequently mutated in NSCLC. In this review, we discuss the effects of EGFR mutants on cell proliferative and survival signals, as well as metabolic reprogramming, in NSCLC. We also discuss the use and mechanisms of action of tyrosine kinase inhibitors (TKIs) that target EGFR-mutants and mediate their inhibitory effects by inducing cell death. Development of resistance to EGFR-TKIs is a problem in the clinic. We further discuss the approaches that are used to overcome this resistance, including the development of fourth-generation EGFR-TKIs. Immunotherapy is not very effective in EGFR-mutant NSCLC. We also discuss possible underlying mechanisms for the inadequate response of EGFR-mutant tumors to immunotherapeutics. Given that mutant EGFR transduces survival signals, and affects cellular metabolism, a better understanding of the crosstalk between mutant EGFR-mediated signals and metabolic reprogramming is expected to facilitate the development of newer personalized therapeutics to manage lung cancer.

摘要翻译： 

肺癌是全球范围内高发病率和高死亡率的主要原因。总体而言，肺癌可分为两大类，包括小细胞肺癌（SCLC）和更为常见的非小细胞肺癌（NSCLC）。肺癌发生、生长和进展的分子机制仍十分复杂。除多种遗传异常外，细胞代谢的改变也参与其中。表皮生长因子受体（EGFR）是一种细胞表面蛋白，在NSCLC中常发生突变。本综述讨论了EGFR突变体在NSCLC中对细胞增殖与生存信号以及代谢重编程的影响。同时探讨了靶向EGFR突变体的酪氨酸激酶抑制剂（TKIs）的应用及其作用机制，这类抑制剂通过诱导细胞死亡介导其抑制效应。EGFR-TKIs耐药性的产生是临床面临的重要问题。我们进一步讨论了克服此类耐药性的策略，包括第四代EGFR-TKIs的研发。免疫疗法在EGFR突变型NSCLC中疗效有限，本文亦探讨了EGFR突变肿瘤对免疫治疗反应不足的潜在机制。鉴于突变型EGFR可转导生存信号并影响细胞代谢，深入理解突变EGFR介导的信号通路与代谢重编程之间的交互作用，将有助于开发更有效的新型个体化疗法以应对肺癌。

原文链接：

Cell Death, Molecular Targeted Therapies, and Metabolic Reprogramming in EGFR-Mutant Lung Cancer