A chronicle review of new techniques that facilitate the understanding and development of optimal individualized therapeutic strategies for chordoma.
A chronicle review of new techniques that facilitate the understanding and development of optimal individualized therapeutic strategies for chordoma.
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有助于理解和制定脊索瘤最佳个体化治疗策略的新技术的编年史回顾
DOI：
10.3389/fonc.2022.1029670
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
脊索瘤是一种罕见的恶性骨肿瘤，主要发生在骶骨和斜坡/颅底。手术切除是脊索瘤的首选治疗方法，但其局部复发率高，预后不佳。与其他常见肿瘤相比，脊索瘤的研究和个体化治疗并不多，部分原因是该病的罕见性和缺乏合适的疾病模型，从而延迟了治疗策略的发现。现代技术的最新进展使人们能够更好地了解包括脊索瘤在内的一些罕见疾病。自21世纪初以来，各种脊索瘤细胞系和动物模型的报道，利用下一代测序（NGS）技术部分揭示了肿瘤发生和发展的内在机制。在这项研究中，我们按时间顺序对脊索瘤模型和相关测序研究进行了系统的概述，从第一个患者来源的脊索瘤细胞系（U-CH1）到各种临床前模型，如患者来源的基于类器官的异种移植（PDX）和患者来源的类器官（PDO）模型。现代测序技术的使用已经发现了被认为是潜在治疗靶点的突变和表达特征，例如Brachyury和过度激活的受体酪氨酸激酶（rtk）的表达。此外，计算和生物信息学技术已经使药物重新定位/重新利用和个体化高通量药物筛选成为可能。这些优势有助于研究和开发针对适应症患者的综合和个性化治疗策略，并将显著改善其近期预后。
Chordoma is a rare malignant bone tumor that mainly occurs in the sacrum and the clivus/skull base. Surgical resection is the treatment of choice for chordoma, but the local recurrence rate is high with unsatisfactory prognosis. Compared with other common tumors, there is not much research and individualized treatment for chordoma, partly due to the rarity of the disease and the lack of appropriate disease models, which delay the discovery of therapeutic strategies. Recent advances in modern techniques have enabled gaining a better understanding of a number of rare diseases, including chordoma. Since the beginning of the 21st century, various chordoma cell lines and animal models have been reported, which have partially revealed the intrinsic mechanisms of tumor initiation and progression with the use of next-generation sequencing (NGS) techniques. In this study, we performed a systematic overview of the chordoma models and related sequencing studies in a chronological manner, from the first patient-derived chordoma cell line (U-CH1) to diverse preclinical models such as the patient-derived organoid-based xenograft (PDX) and patient-derived organoid (PDO) models. The use of modern sequencing techniques has discovered mutations and expression signatures that are considered potential treatment targets, such as the expression of Brachyury and overactivated receptor tyrosine kinases (RTKs). Moreover, computational and bioinformatics techniques have made drug repositioning/repurposing and individualized high-throughput drug screening available. These advantages facilitate the research and development of comprehensive and personalized treatment strategies for indicated patients and will dramatically improve their prognoses in the near feature.
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由脊索驱动的 HRASV12 表达启动的脊索瘤斑马鱼模型。
影响因子：
4.3
作者：
Burger A;Vasilyev A;Tomar R;Selig MK;Nielsen GP;Peterson RT;Drummond IA;Haber DA
通讯作者：
Haber DA
影响因子：
5.6
作者：
Bizon, Chris;Cox, Steven;Tropsha, Alexander
通讯作者：
Tropsha, Alexander
影响因子：
7.4
作者：
Alves, Vinicius M.;Korn, Daniel;Pervitsky, Vera;Thieme, Andrew;Capuzzi, Stephen J.;Baker, Nancy;Chirkova, Rada;Ekins, Sean;Muratov, Eugene N.;Hickey, Anthony;Tropsha, Alexander
通讯作者：
Tropsha, Alexander
影响因子：
3.3
作者：
Zhu GG;Ramirez D;Chen W;Lu C;Wang L;Frosina D;Jungbluth A;Ntiamoah P;Nafa K;Boland PJ;Hameed MR
通讯作者：
Hameed MR
影响因子：
45.3
作者：
Chugh, R;Dunn, R;Baker, LH
通讯作者：
Baker, LH