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基于组学的非小细胞肺癌EGFR-TKIs耐药的分子机制研究进展. (2026). 环球医学研究, 3(4), 129-138. https://doi.org/10.62836/medicine.v3i4.1429
Copyright (c) 2026 袁海宁
This work is licensed under a Creative Commons Attribution 4.0 International License.
基于组学的非小细胞肺癌EGFR-TKIs耐药的分子机制研究进展
袁海宁
杭州医学院检验医学院、生物工程学院，浙江杭州
摘要：晚期非小细胞肺癌（NSCLC）是肺癌最主要的组织亚型，是最恶性的肿瘤之一。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）已彻底改变了NSCLC的治疗策略，是携带EGFR 突变的NSCLC患者的首选药物。然而，ECFR-TKI单药的长期使用因不可避免诱导肿瘤细胞激活多种分子机制出现了耐药，严重影响患者预后。随着组学技术的发展，研究者可以依靠高通量检测技术（基因测序，质谱等）高效、快速地获取肿瘤多层次的生物学信息，为肿瘤相关分子机制的研究奠定了基础。本文系统梳理了基于不同组学（基因组、转录组、表观组学、蛋白质组学，代谢组学等）的EGFR-TKIs治疗NSCLC的耐药分子机制研究的最新应用与进展。深入讨论了不同组学的特点以及在研究肿瘤异质性、识别关键耐药基因与通路中的优势，为未来NSCLC的EGFR-TKIs耐药分子机制研究提供参考。
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[23] Koks G, Pfaff A L, Bubb V J, et al. At the dawn of the transcriptomic medicine [J]. Exp Biol Med (Maywood), 2021, 246(3): 286-92.
[24] Liu D, Lu X, Huang W, et al. Long non-coding RNAs in non- small cell lung cancer: implications for EGFR-TKI resistance [J]. Front Genet, 2023, 14: 1222059.
[25] Wang S, Liu C, Lei Q, et al. Relationship between long non- coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells [J]. Respir Res, 2021, 22(1): 146.
[26] Chen J, Cui J D, Gou X T, et al. Increased expression of miR- 641 contributes to erlotinib resistance in non-small-cell lung cancer cells by targeting NF1 [J]. Cancer Med, 2018, 7(4): 1394-403.
[27] Hisakane K, Seike M, Sugano T, et al. Exosome-derived miR-210 involved in resistance to osimertinib and epithelial- mesenchymal transition in EGFR mutant non-small cell lung cancer cells [J]. Thorac Cancer, 2021, 12(11): 1690-8.
[28] Liu H, Wang S, Zhou S, et al. Drug Resistance-Related Competing Interactions of lncRNA and mRNA across 19 Cancer Types [J]. Mol Ther Nucleic Acids, 2019, 16: 442-51.
[29] Si J, Ma Y, Lv C, et al. HIF1A-AS2 induces osimertinib resistance in lung adenocarcinoma patients by regulating the miR-146b-5p/IL-6/STAT3 axis [J]. Mol Ther Nucleic Acids, 2021, 26: 613-24.
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[31] 夏云秀,董洪亮,刘翠兰等.LINC00973通过hsa-miR-150-5p/ABCG5轴调控非小细胞肺癌多药耐药[J].中国病理生理杂志,2025,41(3):433-43.
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[39] Alsaed B, Lin L, Son J, et al. Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment [J]. Nat Commun, 2025, 16(1): 28.
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[43] Wu Q, Sui X, Tian R. Advances in high-throughput proteomic analysis [J]. Se Pu, 2021, 39(2): 112-7.
[44] Wang Z, Lei P, Li Z, et al. Proteomic and phosphoproteomic analyses reveal the oncogenic role of PTK7-NDRG1 axis in non-small-cell lung cancer cell resistance to AZD9291 [J]. ACS Chem Biol, 2022, 17(10): 2849-62.
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[46] Ma Y, Zhang F, LI J, et al. Diverse perspectives on proteomic posttranslational modifications to address EGFR-TKI resistance in non-small cell lung cancer [J]. Front Cell Dev Biol, 2024, 12: 1436033.
[47] Linder M E, Deschenes R J. Palmitoylation: policing protein stability and traffic [J]. Nat Rev Mol Cell Biol, 2007, 8(1): 74-84.
[48] Cui H, Cai X, Qian Q, et al. ZDHHC11-mediated AXL palmitoylation promotes osimertinib resistance in non-small- cell lung cancer [J]. Proc Natl Acad Sci U S A, 2025, 122(44): e2502778122.
[49] Kumar A, Misra B B. Challenges and opportunities in cancer metabolomics [J]. Proteomics, 2019, 19(21-22): e1900042.
[50] Saorin A, DI Gregorio E, Miolo G, et al. Emerging role of metabolomics in Ovarian Cancer Diagnosis [J]. Metabolites, 2020, 10(10):419.
[51] Njoku K, Sutton C J, Whetton A D, et al. Metabolomic biomarkers for detection, prognosis and identifying recurrence in endometrial cancer [J]. Metabolites, 2020, 10(8): 314.
[52] Araujo R, Bispo D, Helguero L A, et al. Metabolomic studies of breast cancer in murine models: A review [J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(5): 165713.
[53] 肖辛瑶,郭舜尧,陆海艳等.脂质代谢重编程对非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂耐药影响的研究进展[J].中国临床研究,2024,37(1):1-5.
[54] Fang S, Zhu Y, Chen W, et al. NAT10-mediated lipid metabolic reprogramming drives EGFR-TKI resistance in non-small cell lung cancer via ac4C-dependent mRNA stabilization [J]. Exp Hematol Oncol, 2025, 14(1): 134.
[55] Thamlikitkul L, Wanichthanarak K, Manocheewa S, et al. Plasma metabolomic analysis in Thai EGFR-mutated non-small cell lung cancer patients [J]. Comput Struct Biotechnol J, 2025, 27: 4321-31.
[56] 满都花,庄翔,徐佳欢等.EGFR基因突变与非小细胞肺癌CT影像组学特征的相关性研究[J].中国卫生标准管理,2024,15(8):105-109.
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