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多基因检测和孤立肿瘤细胞在早期乳腺癌治疗中的应用:生物网络的时代。

Multigene assays and isolated tumor cells for early breast cancer treatment: time for bionetworks.

机构信息

Department of Surgery, Ioannina University School of Medicine, Ioannina, Greece.

出版信息

Expert Rev Anticancer Ther. 2010 Aug;10(8):1187-95. doi: 10.1586/era.10.91.

Abstract

Despite advances with adjuvant endocrine treatment for hormone receptor-positive tumors and with trastuzumab for HER2-positive disease, overall, over 50% of women with early-stage breast cancer experience recurrence and die of the disease. Biomarkers for tailoring systemic adjuvant treatment to responder patients are needed. The multigene assays, 21-gene recurrence score (Oncotype DX [Genomic Health, CA, USA]) and 70-gene signature (MammaPrint [Agendia, CA, USA]), and the isolated tumor cells in sentinel lymph node(s) represent the latest advances for improving adjuvant chemotherapy decisions. This article evaluates how these new markers, added to current standard factors (age, tumor size, grade, hormone receptor status and HER2 status), could improve early breast cancer treatment decisions. Moreover, emerging evidence from the latest large-scale studies using next-generation DNA-sequencing technology reveals a high heterogeneity and complexity of breast cancer. This assessment now shapes a new research strategy towards completion of a breast cancer causal (driver) mutations catalog and understanding complex genetic interactions and signaling pathway networks. Despite multiple challenges, advances in cancer genomes and systems biology approaches promise the future development of robust biomarkers.

摘要

尽管在激素受体阳性肿瘤的辅助内分泌治疗和曲妥珠单抗治疗 HER2 阳性疾病方面取得了进展,但总体而言,超过 50%的早期乳腺癌女性会出现复发并死于该疾病。需要寻找生物标志物来针对应答者患者进行系统辅助治疗。多基因检测、21 基因复发评分(Oncotype DX [Genomic Health,CA,USA])和 70 基因特征(MammaPrint [Agendia,CA,USA])以及前哨淋巴结中分离的肿瘤细胞是改善辅助化疗决策的最新进展。本文评估了这些新标志物如何与当前的标准因素(年龄、肿瘤大小、分级、激素受体状态和 HER2 状态)相结合,以改善早期乳腺癌的治疗决策。此外,来自最新大规模研究中使用下一代 DNA 测序技术的新兴证据揭示了乳腺癌的高度异质性和复杂性。这种评估现在形成了一种新的研究策略,旨在完成乳腺癌因果(驱动)突变目录,并了解复杂的遗传相互作用和信号通路网络。尽管存在诸多挑战,但癌症基因组和系统生物学方法的进步有望为稳健的生物标志物的未来发展奠定基础。

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