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乳腺恶性叶状肿瘤的最新进展

Recent Advances in Malignant Phyllodes Tumors of the Breast.

作者信息

Lee Eun-Shin

机构信息

Department of Surgery, Korea University Hospital, Korea University College of Medicine, Seoul, Korea.

出版信息

J Breast Cancer. 2025 Apr;28(2):51-60. doi: 10.4048/jbc.2024.0284.

Abstract

Phyllodes tumors (PTs) represent an uncommon category of fibroepithelial neoplasms found in the breast tissue and are classified as benign, borderline, or malignant based on their histopathological features. Histological assessment remains the cornerstone of a PT diagnosis. However, recent genomic advancements have revealed the biological mechanisms underlying PTs, particularly malignant phyllodes tumors (MPTs). This comprehensive review integrates current genomic and molecular investigations that have elucidated the distinguishing features of PTs. Mutations in the gene represent early tumorigenic phenomena that are often observed in benign lesions, whereas modifications in the promoter, alterations in , and amplification of are associated with malignant transformation. Moreover, novel transcriptomic investigations have characterized discrete molecular subtypes exhibiting epithelial and fibrous attributes, thereby enriching our understanding of MPT heterogeneity. Actionable genomic modifications, including dysregulation of the PI3K/Akt/mTOR, MET, and IGF1R signaling cascades, represent promising directions for targeted therapeutic strategies; however, clinical validation is still insufficient. Advances in patient-derived models have created functional platforms conducive to drug screening and preclinical evaluation. Molecular examination has expanded our understanding of PTs, revealing the genomic components linked to malignant progression and identifying prospective therapeutic targets. Nevertheless, obstacles remain in the practical application of these discoveries, primarily owing to the intratumoral heterogeneity and rarity of MPTs. Future investigations should prioritize the integration of diverse omics methodologies, enhancement of preclinical testing frameworks, and establishment of global data-sharing initiatives to promote biomarker-driven treatment strategies.

摘要

叶状肿瘤(PTs)是一种在乳腺组织中发现的罕见的纤维上皮性肿瘤,根据其组织病理学特征分为良性、交界性或恶性。组织学评估仍然是PT诊断的基石。然而,最近的基因组进展揭示了PTs,特别是恶性叶状肿瘤(MPTs)的生物学机制。这篇综述整合了当前的基因组和分子研究,阐明了PTs的显著特征。基因中的突变代表了早期致瘤现象,常在良性病变中观察到,而启动子的修饰、基因的改变和基因的扩增与恶性转化相关。此外,新的转录组学研究已经确定了表现出上皮和纤维特征的离散分子亚型,从而丰富了我们对MPT异质性的理解。可操作的基因组修饰,包括PI3K/Akt/mTOR、MET和IGF1R信号级联的失调,代表了靶向治疗策略的有前景的方向;然而,临床验证仍然不足。患者来源模型的进展创造了有利于药物筛选和临床前评估的功能平台。分子检测扩展了我们对PTs的理解,揭示了与恶性进展相关的基因组成分,并确定了潜在的治疗靶点。然而,这些发现的实际应用仍然存在障碍,主要是由于MPTs的肿瘤内异质性和罕见性。未来的研究应优先整合多种组学方法,加强临床前测试框架,并建立全球数据共享倡议,以促进生物标志物驱动的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be28/12046350/bf93c077b63a/jbc-28-51-g001.jpg

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