Epigenetic code underlying EGFR-TKI resistance in non-small cell lung cancer: Elucidation of mechanisms and perspectives on therapeutic strategies

被引：2
作者：
Yao, Xiaoyu [1 ]
Gao, Chundi [2 ]
Sun, Changgang [2 ,3 ]
Chen, Zhe-Sheng [4 ]
Zhuang, Jing [3 ]
机构：
[1] Shandong Univ Tradit Chinese Med, Coll Clin Med 1, Jinan, Peoples R China
[2] Shandong Second Med Univ, Coll Tradit Chinese Med, Weifang, Peoples R China
[3] Weifang Tradit Chinese Hosp, Dept Oncol, Weifang, Peoples R China
[4] St Johns Univ, Coll Pharm & Hlth Sci, Jamaica, NY 11432 USA
来源：
DRUG DISCOVERY TODAY | 2025年 / 30卷 / 03期
基金：
中国国家自然科学基金;
关键词：
Tumor drug resistance; EGFR-TKI; Epigenetics; Biomarkers; Combined therapy; TYROSINE KINASE INHIBITORS; GEFITINIB-RESISTANCE; ACQUIRED-RESISTANCE; HISTONE DEACETYLASES; DRUG-RESISTANCE; ERLOTINIB RESISTANCE; DNA METHYLATION; OSIMERTINIB RESISTANCE; MESENCHYMAL TRANSITION; ADENOCARCINOMA CELLS;
D O I：
10.1016/j.drudis.2025.104321
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Non-small-cell lung cancer (NSCLC) is the most common lung cancer subtype, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the core drugs used for its treatment. However, the emergence of drug resistance poses a significant challenge to their clinical efficacy. As a significant role-player in cancer development and maintenance, histone modifications, DNA methylation and noncoding RNA (ncRNA) changes have been proven to play a crucial part in driving EGFR-TKI resistance, which provides promising potential therapeutic targets and biomarkers for overcoming drug resistance. This review delves into the complex epigenetic mechanisms that cause EGFR-TKI resistance and emphasizes the potential of combined epigenetic therapies, aiming to provide better-targeted treatment options for NSCLC patients with NSCLC and drive innovative strategies to overcome the challenges of drug resistance.
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页数：17
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共 208 条
[1]   A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy [J].
Ayati, Adileh ;
Moghimi, Setareh ;
Salarinejad, Somayeh ;
Safavi, Maliheh ;
Pouramiri, Behjat ;
Foroumadi, Alireza .
BIOORGANIC CHEMISTRY, 2020, 99
[2]   BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells [J].
Bach, Duc-Hiep ;
Thi-Thu-Trang Luu ;
Kim, Donghwa ;
An, Yong Jin ;
Park, Sunghyouk ;
Park, Hyen Joo ;
Lee, Sang Kook .
MOLECULAR THERAPY-NUCLEIC ACIDS, 2018, 12 :817-828
[3]   Histone deacetylases and cancer [J].
Barneda-Zahonero, Bruna ;
Parra, Maribel .
MOLECULAR ONCOLOGY, 2012, 6 (06) :579-589
[4]   Long noncoding RNAs in cancer: mechanisms of action and technological advancements [J].
Bartonicek, Nenad ;
Maag, Jesper L. V. ;
Dinger, Marcel E. .
MOLECULAR CANCER, 2016, 15
[5]   miR-19b enhances proliferation and apoptosis resistance via the EGFR signaling pathway by targeting PP2A and BIM in non-small cell lung cancer [J].
Baumgartner, Ulrich ;
Berger, Fabienne ;
Gheinani, Ali Hashemi ;
Burgener, Sabrina Sofia ;
Monastyrskaya, Katia ;
Vassella, Erik .
MOLECULAR CANCER, 2018, 17
[6]   FOXO3-induced oncogenic lncRNA CASC9 enhances gefitinib resistance of non-small-cell lung cancer through feedback loop [J].
Bing, Zhongxing ;
Han, Jiashu ;
Zheng, Zhibo ;
Liang, Naixin .
LIFE SCIENCES, 2021, 287
[7]   Systemic delivery of aptamer-drug conjugates for cancer therapy using enzymatically generated self-assembled DNA nanoparticles [J].
Binh Thanh Tran ;
Kim, Junghyun ;
Ahn, Dae-Ro .
NANOSCALE, 2020, 12 (45) :22945-22951
[8]   Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J].
Bray, Freddie ;
Laversanne, Mathieu ;
Sung, Hyuna ;
Ferlay, Jacques ;
Siegel, Rebecca L. ;
Soerjomataram, Isabelle ;
Jemal, Ahmedin .
CA-A CANCER JOURNAL FOR CLINICIANS, 2024, 74 (03) :229-263
[9]   Adjuvant and Neoadjuvant Immunotherapy in Non - small Cell Lung Cancer [J].
Broderick, Stephen R. .
THORACIC SURGERY CLINICS, 2020, 30 (02) :215-+
[10]   Amphiregulin Promotes Resistance to Gefitinib in NonSmall Cell Lung Cancer Cells by Regulating Ku70 Acetylation [J].
Busser, Benoit ;
Sancey, Lucie ;
Josserand, Veronique ;
Niang, Carole ;
Khochbin, Saadi ;
Favrot, Marie C. ;
Coll, Jean-Luc ;
Hurbin, Amandine .
MOLECULAR THERAPY, 2010, 18 (03) :536-543
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