进化概述和未来展望:ESR1突变、液体活检和人工智能在ER+乳腺癌个体化医疗新时代的应用。

IF 4.4 3区 医学 Q1 GENETICS & HEREDITY
Serafina Martella, Giacomo Cusumano, Thilini Hemali Senevirathne, Dimitrios Stylianakis, Enrico Palmas, Nerina Denaro, Chiara Tommasi, Mario Scartozzi, Lorenzo Gerratana, Cinzia Solinas
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引用次数: 0

摘要

ESR1基因突变是雌激素受体阳性(ER+)乳腺癌获得性内分泌治疗耐药(ET)的主要机制之一。液体活检作为一种分析循环肿瘤DNA (ctDNA)的微创技术的引入,为实时突变监测和个性化治疗策略开辟了新的途径。本综述探讨了ESR1突变在内分泌抵抗中的临床意义,液体活检在早期检测和监测中的潜力,以及先进测序技术和人工智能的结合以提高诊断准确性。分析关键突变(D538G、Y537S)的临床前和临床研究,比较新兴技术(下一代测序(NGS)、数字液滴PCR (ddPCR)、深度测序癌症个性化分析(CAPP-Seq)、靶向数字测序(TARDIS)),总结7项主要研究的生存数据,评估ESR1突变对无进展生存期(PFS)和总生存期(OS)的影响。结果表明,这些突变,特别是那些影响配体结合域的突变,与芳香酶抑制剂的疗效降低和肿瘤侵袭性增加有关。液体活检被证明对耐药突变的早期检测和动态疾病监测是有用的,但其临床实施受到ctDNA水平低、技术可变性和缺乏标准化临床切断的限制。与组织活检、放射组学和基于人工智能(AI)的平台相结合,增强了其临床应用和预后价值。总之,液体活检,当与先进技术和预测工具相结合时,代表了ER+乳腺癌个性化管理的创新资源,具有指导及时治疗干预和提高长期生存率的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evolutionary Overview and Future Perspectives: ESR1 Mutations, Liquid Biopsy, and Artificial Intelligence for a New Era of Personalized Medicine in ER+ Breast Cancer.

ESR1 gene mutations represent one of the main mechanisms of acquired resistance to endocrine therapy (ET) in estrogen receptor-positive (ER+) breast cancer. The introduction of liquid biopsy as a minimally invasive technique for analyzing circulating tumor DNA (ctDNA) has opened new avenues for real-time mutation monitoring and personalized treatment strategies. This review explores the clinical relevance of ESR1 mutations in endocrine resistance, the potential of liquid biopsy for early detection and monitoring, and the integration of advanced sequencing technologies and artificial intelligence to improve diagnostic accuracy. Preclinical and clinical studies on key mutations (D538G, Y537S) were analyzed, emerging technologies [(next-generation sequencing (NGS), digital droplet PCR (ddPCR), Cancer Personalized Profiling by deep Sequencing (CAPP-Seq), Targeted Digital Sequencing (TARDIS)] were compared, and survival data from seven major studies were summarized to assess the impact of ESR1 mutations on progression-free survival (PFS) and overall survival (OS). The results show that these mutations, particularly those affecting the ligand-binding domain, are associated with reduced efficacy of aromatase inhibitors and increased tumor aggressiveness. Liquid biopsy proves useful for early detection of resistance mutations and dynamic disease monitoring, but its clinical implementation is limited by low ctDNA levels, technological variability, and the lack of standardized clinical cut-offs. Integration with tissue biopsy, radiomics, and artificial intelligence (AI)-based platforms enhances its clinical utility and prognostic value. In conclusion, liquid biopsy, when combined with advanced technologies and predictive tools, represents an innovative resource for the personalized management of ER+ breast cancer, with the potential to guide timely therapeutic interventions and improve long-term survival.

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来源期刊
CiteScore
7.80
自引率
2.50%
发文量
53
审稿时长
>12 weeks
期刊介绍: Molecular Diagnosis & Therapy welcomes current opinion articles on emerging or contentious issues, comprehensive narrative reviews, systematic reviews (as outlined by the PRISMA statement), original research articles (including short communications) and letters to the editor. All manuscripts are subject to peer review by international experts.
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