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精准出击:胸膜间皮瘤靶向治疗方法综述。

Unleashing precision: A review of targeted approaches in pleural mesothelioma.

机构信息

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

出版信息

Crit Rev Oncol Hematol. 2024 Nov;203:104481. doi: 10.1016/j.critrevonc.2024.104481. Epub 2024 Aug 17.

DOI:10.1016/j.critrevonc.2024.104481
PMID:39159705
Abstract

This review delves into the intricate landscape of pleural mesothelioma (PM), emphasizing the need for nuanced therapeutic strategies. While platinum-based chemotherapy remains a cornerstone, the advent of immune checkpoint inhibitors (ICIs), notably through the Checkmate 743 trial, has reshaped treatment paradigms. Challenges persist due to patient heterogeneity and a lack of specific biomarkers. Targeting genotypic and phenotypic alterations emerges as a promising avenue, demanding precision oncology in this rare disease. CDKN2A loss, prevalent in PM, may respond to CDK4/6 inhibitors. Defects in MMR and HR suggest tailored approaches with ICI or PARP inhibitors, respectively. Ongoing trials explore novel inhibitors and promising targets like mesothelin. Implementing these strategies requires overcoming challenges in patient selection, combination therapies, biomarker identification, and cost considerations. Collaboration is crucial for transforming these insights into impactful clinical interventions, heralding the era of personalized and precision medicine for PM.

摘要

这篇综述深入探讨了胸膜间皮瘤(PM)的复杂情况,强调需要制定细致的治疗策略。铂类化疗仍然是基石,但免疫检查点抑制剂(ICI)的出现,特别是通过 Checkmate 743 试验,已经改变了治疗模式。由于患者的异质性和缺乏特异性生物标志物,挑战仍然存在。针对基因型和表型改变是一个很有前途的途径,这在这种罕见疾病中需要精准肿瘤学。在 PM 中常见的 CDKN2A 缺失可能对 CDK4/6 抑制剂有反应。MMR 和 HR 缺陷分别提示使用 ICI 或 PARP 抑制剂进行针对性治疗。正在进行的试验探索新型抑制剂和有前途的靶点,如间皮素。实施这些策略需要克服患者选择、联合治疗、生物标志物识别和成本考虑方面的挑战。合作对于将这些见解转化为有影响力的临床干预至关重要,标志着 PM 个体化和精准医学的时代已经到来。

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MedComm (2020). 2025 Sep 1;6(9):e70327. doi: 10.1002/mco2.70327. eCollection 2025 Sep.
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[Recent Advances in Medical Treatment of Malignant Pleural Mesothelioma].[恶性胸膜间皮瘤的医学治疗新进展]
Zhongguo Fei Ai Za Zhi. 2025 May 20;28(5):391-399. doi: 10.3779/j.issn.1009-3419.2025.102.18.
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Malignant mesothelioma-associated inflammatory microenvironment promotes tumor progression via GPNMB.
恶性间皮瘤相关的炎性微环境通过GPNMB促进肿瘤进展。
J Transl Med. 2025 Apr 18;23(1):454. doi: 10.1186/s12967-025-06407-4.
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J Exp Clin Cancer Res. 2024 Dec 21;43(1):327. doi: 10.1186/s13046-024-03253-y.