Advantages and Challenges of Using ctDNA NGS to Assess the Presence of Minimal Residual Disease (MRD) in Solid Tumors.
Advantages and Challenges of Using ctDNA NGS to Assess the Presence of Minimal Residual Disease (MRD) in Solid Tumors.
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DOI：
10.3390/cancers13225698
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发表时间：
2021-11-14
期刊：
影响因子：
5.2
通讯作者：
Martens UM
中科院分区：
文献类型：
--
作者：
Larribère L;Martens UM
微小残留病（MRD）代表一种疾病状态，在通过放射学进行临床观察之前，假定该疾病仍然存在于体内。此时，肿瘤复发，应做出新的临床决定。然而，目前还没有官方的生物标志物可以有效预测治愈性手术或治疗后的复发。这种未满足的临床需求将从这样的生物标志物中受益，因为它将有助于指导辅助治疗的决策。使用液体活检技术来测量患者血液中的非侵入性循环肿瘤 DNA (ctDNA) 的可能性，为建立这种生物标记物开辟了新途径。在这篇综述中，我们总结了目前关于 NGS ctDNA 检测作为评估 MRD 存在的工具的知识，以及侧重于该方法的临床实用性的临床试验。在治愈性手术或治疗后检测微小残留病 (MRD) 的能力至关重要，因为它提供了帮助指导与辅助治疗相关的临床决策的可能性。因此，越早检测到 MRD，就能越早向可能需要的患者提出潜在有益的治疗。液体活检，特别是血液中循环肿瘤 DNA (ctDNA) 的新一代测序，已成为过去几年越来越多研究的焦点。晚期癌症阶段的 ctDNA 检测适用于多种实体瘤，并补充了获得性治疗耐药性的分子信息。在 MRD 的背景下，从定义上来说，检测 ctDNA 更具挑战性，但它在技术上是可以实现的，并且比标准成像方法更早地提供有关治疗反应和复发概率的信息。目前正在介入临床试验中测试在常规中实施这项新技术的临床益处。我们在此建议更新目前使用 NGS ctDNA 检测作为评估 MRD 存在和改善实体瘤辅助治疗的工具。我们还讨论了该过程在临床中的主要局限性和中期前景。
Minimal residual disease (MRD) represents a status of the disease which is assumed to still be present in the body until it is clinically observed by radiology. At this time point, the tumor relapse is present and a new clinical decision should be taken. However, there is currently no official biomarker which can efficiently predict a relapse after a curative-intent surgery or treatment. This unmet clinical need would benefit from such a biomarker as it would help guiding the decision on adjuvant therapy. The possibility to use the liquid biopsy technology in order to measure non-invasive circulating tumor DNA (ctDNA) in the patient’s blood opens a new avenue to the establishment of this biomarker. In this review we summarize the current knowledge on ctDNA detection by NGS as a tool to assess the presence of MRD as well as the clinical trials focusing on the clinical utility of the method. The ability to detect minimal residual disease (MRD) after a curative-intent surgery or treatment is of paramount importance, because it offers the possibility to help guide the clinical decisions related adjuvant therapy. Thus, the earlier MRD is detected, the earlier potentially beneficial treatment can be proposed to patients who might need it. Liquid biopsies, and in particular the next-generation sequencing of circulating tumor DNA (ctDNA) in the blood, have been the focus of an increasing amount of research in the past years. The ctDNA detection at advanced cancer stages is practicable for several solid tumors, and complements molecular information on acquired therapy resistance. In the context of MRD, it is by definition more challenging to detect ctDNA, but it is technically achievable and provides information on treatment response and probability of relapse significantly earlier than standard imaging methods. The clinical benefit of implementing this new technique in the routine is being tested in interventional clinical trials at the moment. We propose here an update of the current use of ctDNA detection by NGS as a tool to assess the presence of MRD and improve adjuvant treatment of solid tumors. We also discuss the main limitations and medium-term perspectives of this process in the clinic.
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影响因子：
82.9
作者：
Fairfax BP;Taylor CA;Watson RA;Nassiri I;Danielli S;Fang H;Mahé EA;Cooper R;Woodcock V;Traill Z;Al-Mossawi MH;Knight JC;Klenerman P;Payne M;Middleton MR
通讯作者：
Middleton MR
DOI：
10.1093/annonc/mdx112
发表时间：
2017-06-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Grasselli J;Elez E;Caratù G;Matito J;Santos C;Macarulla T;Vidal J;Garcia M;Viéitez JM;Paéz D;Falcó E;Lopez Lopez C;Aranda E;Jones F;Sikri V;Nuciforo P;Fasani R;Tabernero J;Montagut C;Azuara D;Dienstmann R;Salazar R;Vivancos A
通讯作者：
Vivancos A
影响因子：
28.4
作者：
Garcia-Murillas, Isaac;Chopra, Neha;Turner, Nicholas C.
通讯作者：
Turner, Nicholas C.
影响因子：
64.8
作者：
Abbosh C;Birkbak NJ;Wilson GA;Jamal-Hanjani M;Constantin T;Salari R;Le Quesne J;Moore DA;Veeriah S;Rosenthal R;Marafioti T;Kirkizlar E;Watkins TBK;McGranahan N;Ward S;Martinson L;Riley J;Fraioli F;Al Bakir M;Grönroos E;Zambrana F;Endozo R;Bi WL;Fennessy FM;Sponer N;Johnson D;Laycock J;Shafi S;Czyzewska-Khan J;Rowan A;Chambers T;Matthews N;Turajlic S;Hiley C;Lee SM;Forster MD;Ahmad T;Falzon M;Borg E;Lawrence D;Hayward M;Kolvekar S;Panagiotopoulos N;Janes SM;Thakrar R;Ahmed A;Blackhall F;Summers Y;Hafez D;Naik A;Ganguly A;Kareht S;Shah R;Joseph L;Marie Quinn A;Crosbie PA;Naidu B;Middleton G;Langman G;Trotter S;Nicolson M;Remmen H;Kerr K;Chetty M;Gomersall L;Fennell DA;Nakas A;Rathinam S;Anand G;Khan S;Russell P;Ezhil V;Ismail B;Irvin-Sellers M;Prakash V;Lester JF;Kornaszewska M;Attanoos R;Adams H;Davies H;Oukrif D;Akarca AU;Hartley JA;Lowe HL;Lock S;Iles N;Bell H;Ngai Y;Elgar G;Szallasi Z;Schwarz RF;Herrero J;Stewart A;Quezada SA;Peggs KS;Van Loo P;Dive C;Lin CJ;Rabinowitz M;Aerts HJWL;Hackshaw A;Shaw JA;Zimmermann BG;TRACERx consortium;PEACE consortium;Swanton C
通讯作者：
Swanton C
影响因子：
11.5
作者：
Georgiadis, Andrew;Durham, Jennifer N.;Sausen, Mark
通讯作者：
Sausen, Mark