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转移性肾细胞癌下一代测序分析的前瞻性单中心试验:MORE-TRIAL试验

Prospective single center trial of next-generation sequencing analysis in metastatic renal cell cancer: the MORE-TRIAL.

作者信息

Dieffenbacher Svenja, Zschäbitz Stefanie, Hofer Luisa, Hatiboglu Gencay, Hou Weibin, Hohenfellner Markus, Duensing Stefan, Sültmann Holger, Pahernik Sascha, Grüllich Carsten

机构信息

The Renal Cancer Center at the National Center for Tumor Diseases (NCT) Heidelberg, Germany, Department of Urology, Heidelberg University Hospital, Im Neuenheimer Feld 110, Heidelberg, Germany.

The Renal Cancer Center at the National Center for Tumor Diseases (NCT) Heidelberg, Germany, Department of Medical Oncology, National Center for Tumor Diseases Heidelberg, Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany.

出版信息

Future Sci OA. 2018 Mar 14;4(5):FSO299. doi: 10.4155/fsoa-2017-0150. eCollection 2018 Jun.

DOI:10.4155/fsoa-2017-0150
PMID:29796302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5961447/
Abstract

AIM

Targeted therapies have substantially improved the survival of patients with metastatic clear cell renal cell cancer. No prognostic or predictive biomarkers are available. Comprehensive genetic profiling offers the opportunity to define prognostic and predictive signatures aiming at a more personalized approach to treatment.

METHODS

In this prospectively conducted cohort study, tumor tissue and liquid biopsies are sampled at baseline and upon first and second progression under systemic treatment. Samples will be analyzed by whole-exome sequencing to generate prognostic and predictive patterns for systemic therapies.

DISCUSSION

This study is aiming at exploring genetic profiles with prognostic and predictive value in metastatic renal cell cancer patients. Clonal evolution facilitating resistance to systemic treatment will be investigated by repeat biopsies.

摘要

目的

靶向治疗显著提高了转移性透明细胞肾细胞癌患者的生存率。目前尚无预后或预测生物标志物。全面的基因分析提供了定义预后和预测特征的机会,旨在实现更个性化的治疗方法。

方法

在这项前瞻性队列研究中,在基线时以及全身治疗的首次和第二次病情进展时采集肿瘤组织和液体活检样本。样本将通过全外显子测序进行分析,以生成全身治疗的预后和预测模式。

讨论

本研究旨在探索转移性肾细胞癌患者具有预后和预测价值的基因特征。将通过重复活检研究促进对全身治疗耐药的克隆进化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9115/5961447/0cfdb688350f/fsoa-04-299-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9115/5961447/1095791b9a5f/fsoa-04-299-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9115/5961447/0cfdb688350f/fsoa-04-299-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9115/5961447/1095791b9a5f/fsoa-04-299-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9115/5961447/0cfdb688350f/fsoa-04-299-g2.jpg

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本文引用的文献

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Patient-specific molecular alterations are associated with metastatic clear cell renal cell cancer progressing under tyrosine kinase inhibitor therapy.患者特异性分子改变与在酪氨酸激酶抑制剂治疗下进展的转移性透明细胞肾细胞癌相关。
Oncotarget. 2017 May 23;8(43):74049-74057. doi: 10.18632/oncotarget.18200. eCollection 2017 Sep 26.
2
Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.肾细胞癌:ESMO 诊断、治疗及随访临床实践指南
Ann Oncol. 2016 Sep;27(suppl 5):v58-v68. doi: 10.1093/annonc/mdw328.
3
Mutation analysis of circulating plasma DNA to determine response to EGFR tyrosine kinase inhibitor therapy of lung adenocarcinoma patients.
检测循环血浆 DNA 突变分析以确定肺腺癌患者对表皮生长因子受体酪氨酸激酶抑制剂治疗的反应。
Sci Rep. 2016 Sep 19;6:33505. doi: 10.1038/srep33505.
4
Low Input Whole-Exome Sequencing to Determine the Representation of the Tumor Exome in Circulating DNA of Non-Small Cell Lung Cancer Patients.低投入全外显子组测序以确定非小细胞肺癌患者循环DNA中肿瘤外显子组的表现
PLoS One. 2016 Aug 16;11(8):e0161012. doi: 10.1371/journal.pone.0161012. eCollection 2016.
5
Spatial niche formation but not malignant progression is a driving force for intratumoural heterogeneity.空间生态位形成而非恶性进展是肿瘤异质性形成的驱动力。
Nat Commun. 2016 Jun 13;7:ncomms11845. doi: 10.1038/ncomms11845.
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