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信号通路作为通过上调SOX2在肿瘤细胞中顺铂耐药的关键调节因子。

Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.

作者信息

Taghehchian Negin, Akhlaghipour Iman, Zangouei Amir Sadra, Palizkaran Yazdi Mahsa, Moghbeli Meysam

机构信息

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Med Oncol. 2025 Aug 22;42(10):437. doi: 10.1007/s12032-025-03004-9.

DOI:10.1007/s12032-025-03004-9
PMID:40844657
Abstract

Chemotherapy is one of the first-line treatment options in cancer patients. Cisplatin (CDDP) is widely used as one of the antineoplastic agents in many cancers. Nevertheless, CDDP resistance is considered as a therapeutic challenge in cancer. Considering the CDDP side effects in normal tissues, prediction of CDDP response helps to select a suitable therapeutic strategy in cancer patients. Sex-determining region Y-box 2 (SOX2) is a critical regulator of tumor growth and embryogenesis that is involved in tumor metastasis, apoptosis, and cell proliferation, through association with other developmental/oncogenic signaling pathways. SOX2 has also a crucial role in CDDP resistance in tumor cells. Therefore, we discussed the role of SOX2 in regulation of CDDP response in tumor cells. It has been reported that SOX2 upregulation through PI3K/AKT, WNT, Hippo, and TGF-β signaling pathways mainly promotes the CDDP resistance in tumor cells. The present review can be an effective step in introducing SOX2 as a prognostic marker as well as a therapeutic target in cancer patients.

摘要

化疗是癌症患者的一线治疗选择之一。顺铂(CDDP)作为一种抗肿瘤药物,在许多癌症中被广泛使用。然而,顺铂耐药被认为是癌症治疗中的一项挑战。考虑到顺铂对正常组织的副作用,预测顺铂反应有助于为癌症患者选择合适的治疗策略。性别决定区Y盒2(SOX2)是肿瘤生长和胚胎发育的关键调节因子,通过与其他发育/致癌信号通路相关联,参与肿瘤转移、凋亡和细胞增殖。SOX2在肿瘤细胞的顺铂耐药中也起着关键作用。因此,我们讨论了SOX2在调节肿瘤细胞顺铂反应中的作用。据报道,通过PI3K/AKT、WNT、Hippo和TGF-β信号通路上调SOX2主要促进肿瘤细胞的顺铂耐药。本综述可能是将SOX2作为癌症患者预后标志物和治疗靶点引入的有效一步。

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本文引用的文献

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Bone Res. 2025 Feb 24;13(1):25. doi: 10.1038/s41413-024-00395-9.
2
Aptamer-conjugated gold nanoparticles enable oligonucleotide delivery into muscle stem cells to promote regeneration of dystrophic muscles.适配体偶联的金纳米颗粒可使寡核苷酸递送至肌肉干细胞,以促进营养不良肌肉的再生。
Nat Commun. 2025 Jan 10;16(1):577. doi: 10.1038/s41467-024-55223-9.
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Long non-coding RNAs as the pivotal regulators of epithelial mesenchymal transition through WNT/β-catenin signaling pathway in tumor cells.
长非编码 RNA 通过 WNT/β-连环蛋白信号通路作为肿瘤细胞上皮间质转化的关键调控因子。
Pathol Res Pract. 2024 Nov;263:155683. doi: 10.1016/j.prp.2024.155683. Epub 2024 Oct 28.
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Unveiling the mechanisms and challenges of cancer drug resistance.揭示癌症药物耐药性的机制和挑战。
Cell Commun Signal. 2024 Feb 12;22(1):109. doi: 10.1186/s12964-023-01302-1.
5
Pan-Cancer Analysis Reveals SOX2 as a Promising Prognostic and Immunotherapeutic Biomarker Across Various Cancer Types, Including Pancreatic Cancer.泛癌分析揭示SOX2是包括胰腺癌在内的多种癌症类型中一种有前景的预后和免疫治疗生物标志物。
J Cancer. 2024 Jan 1;15(1):251-274. doi: 10.7150/jca.88397. eCollection 2024.
6
Cancer metastasis: Molecular mechanisms and clinical perspectives.癌症转移:分子机制与临床视角。
Pharmacol Ther. 2023 Oct;250:108522. doi: 10.1016/j.pharmthera.2023.108522. Epub 2023 Sep 1.
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