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基于新一代测序的靶向骨肉瘤治疗的新兴发现。

Emerging next-generation sequencing-based discoveries for targeted osteosarcoma therapy.

机构信息

First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, China; Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA; Department of Orthopaedic Surgery, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, Shandong, 250031, China.

Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.

出版信息

Cancer Lett. 2020 Apr 1;474:158-167. doi: 10.1016/j.canlet.2020.01.020. Epub 2020 Jan 24.

Abstract

Osteosarcoma (OS) is the most common primary bone malignancy and is frequently lethal via metastasis to the lung. While surgical techniques and adjuvant chemotherapies have emerged to combat this deadly cancer, the 5-year survival rate has plateaued over the past four decades. Therapeutic progress has been notably poor because past technologies have not been able to reveal obscured OS biomarkers and targets. With the advent and implementation of large-scale next-generation sequencing (NGS) studies, various somatic mutations and copy number changes involved in OS progression and metastasis have surfaced. These findings have significantly expanded the amount of genome-informed pathways and candidate genes suitable for targeting in pre-clinical models. Furthermore, NGS analyses comparing primary and matched pulmonary metastatic tumor tissues have catalogued previously unknown prognostic biomarkers in OS. In this review, we delineate the most recent findings in NGS for OS therapy and how this technology has advanced personalized therapy.

摘要

骨肉瘤(OS)是最常见的原发性骨恶性肿瘤,通过肺转移常常是致命的。虽然已经出现了外科技术和辅助化疗来治疗这种致命的癌症,但在过去的四十年中,5 年生存率已经趋于稳定。治疗进展明显不佳,因为过去的技术无法揭示隐藏的 OS 生物标志物和靶点。随着大规模下一代测序(NGS)研究的出现和实施,涉及 OS 进展和转移的各种体细胞突变和拷贝数变化已经浮现。这些发现极大地扩展了适用于临床前模型靶向的基于基因组的途径和候选基因数量。此外,比较原发性和匹配的肺转移瘤组织的 NGS 分析已经在 OS 中列出了以前未知的预后生物标志物。在这篇综述中,我们描述了 NGS 在 OS 治疗中的最新发现,以及这项技术如何推动了个性化治疗。

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