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上皮-间质转化在恶性胸膜间皮瘤中的作用:从发病机制到诊断与治疗

The Role of Epithelial-Mesenchymal Transition in Malignant Pleural Mesothelioma: From Pathogenesis to Diagnosis and Treatment.

作者信息

Magouliotis Dimitrios E, Minervini Fabrizio, Cioffi Ugo, De Simone Matilde, Patrini Davide, Scarci Marco

机构信息

Department of Cardiac Surgery Research, Lankenau Institute for Medical Research, Main Line Health, Wynnewood, PA 19096, USA.

Luzern Kanton Hospital, 6000 Luzern, Switzerland.

出版信息

Cells. 2025 Apr 12;14(8):585. doi: 10.3390/cells14080585.

DOI:10.3390/cells14080585
PMID:40277909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12025386/
Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural lining, primarily associated with asbestos exposure. Despite advancements in multimodal treatment, patient survival remains poor. Epithelial-mesenchymal transition (EMT) has emerged as a crucial process driving MPM pathogenesis, metastasis, and resistance to therapy. This review explores the molecular mechanisms underlying EMT in MPM, including key signaling pathways such as TGF-β, Wnt/β-catenin, and PI3K/Akt. We also discuss the diagnostic and prognostic significance of EMT-related biomarkers and emerging targeted therapies aimed at reversing EMT or exploiting EMT-induced vulnerabilities. Additionally, recent clinical trials, including the MARS 2 trial, are reviewed to provide insight into the evolving treatment landscape.

摘要

恶性胸膜间皮瘤(MPM)是一种侵袭性的胸膜内衬癌症,主要与接触石棉有关。尽管多模式治疗取得了进展,但患者生存率仍然很低。上皮-间质转化(EMT)已成为驱动MPM发病机制、转移和治疗耐药性的关键过程。本综述探讨了MPM中EMT的分子机制,包括TGF-β、Wnt/β-连环蛋白和PI3K/Akt等关键信号通路。我们还讨论了EMT相关生物标志物的诊断和预后意义,以及旨在逆转EMT或利用EMT诱导的脆弱性的新兴靶向治疗。此外,还对包括MARS 2试验在内的近期临床试验进行了综述,以深入了解不断演变的治疗格局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b289/12025386/89193a07c4a1/cells-14-00585-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b289/12025386/f5baa2c85ec0/cells-14-00585-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b289/12025386/89193a07c4a1/cells-14-00585-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b289/12025386/f5baa2c85ec0/cells-14-00585-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b289/12025386/89193a07c4a1/cells-14-00585-g002.jpg

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本文引用的文献

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A Perspective on the MARS2 Trial.关于MARS2试验的观点。
J Thorac Oncol. 2025 Mar;20(3):262-272. doi: 10.1016/j.jtho.2024.12.014. Epub 2025 Jan 8.
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Targeted Therapy in Mesotheliomas: Uphill All the Way.间皮瘤的靶向治疗:一路艰难前行。
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Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.广泛胸膜切除术和化疗与单纯化疗治疗胸膜间皮瘤(MARS 2):一项 3 期随机对照试验。
Lancet Respir Med. 2024 Jun;12(6):457-466. doi: 10.1016/S2213-2600(24)00119-X. Epub 2024 May 10.
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Emerging New Targets in Systemic Therapy for Malignant Pleural Mesothelioma.恶性胸膜间皮瘤全身治疗中的新兴新靶点
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