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晚期乳腺癌是严重威胁全世界女性健康的第一大恶性肿瘤,目前以综合治疗为主,包括化疗、内分泌治疗和靶向治疗等。短期内复发、转移是限制临床疗效和导致患者预后差的重要因素,而影像学检查和传统血清标记物却难以及时有效地监测肿瘤的复发转移,导致临床治疗决策迟滞。因此,研发灵敏、准确、非/低侵入性的疗效监测方法 至关重要。循环肿瘤DNA(ctDNA)是游离于血浆中的来源于肿瘤细胞的坏死、凋亡和分泌过程的DNA。多项研究证实检测ctDNA突变水平变化对于恶性肿瘤早期诊断、用药指导、复发监测有着巨大的应用潜力。本文将对ctDNA监测晚期乳腺癌的临床应用研究进展综述如下。 相似文献
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乳腺癌是女性癌症死亡最主要的原因,居女性恶性肿瘤发病率首位。对乳腺癌患者进行早期诊断以及更精准的疗效评估和复发监测,可为患者制定及时有效的个体化治疗方案提供更多的循证依据。本文就循环肿瘤细胞(circulating tumor cells,CTCs)、循环肿瘤DNA(ciculating tumor,ctDNA)、外泌体(Exosomes)、ctDNA甲基化以及循环肿瘤血小板(tumor-educated platelets,TEPs)等循环肿瘤标志物在乳腺癌复发监测和病情评估中的研究进展进行综述。 相似文献
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恶性黑色素瘤(MM)是一种高侵袭性、高致死率的恶性肿瘤。液体活检由于具有样本易获得和创伤性低等优势,在恶性肿瘤诊断和监测中的重要性日益凸显,循环肿瘤DNA(ctDNA)检测正是其中一项新兴起的检测手段。ctDNA在MM诊断和治疗中的临床应用范围十分广泛,包括早期筛查MM人群、帮助检测MM的可驱动基因、监测和评判肿瘤的复发与转移、预测患者对靶向和免疫治疗的反应等。多项研究表明,无论是肿瘤术后辅助治疗还是晚期治疗的肿瘤患者,ctDNA能更好地反映肿瘤的异质性,提供预后相关信息,更早判断疾病的复发与转移,能准确评估对治疗的反应并确定耐药机制等。虽然目前尚未出现基于ctDNA的MM诊治共识,相关研究结论仍需要在前瞻性临床试验中继续验证,但是ctDNA检测为MM患者的临床管理提供了新的选择,不久或将用于进一步完善MM的诊断和治疗。 相似文献
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随着恶性肿瘤精准化诊疗理念的不断深入,在从微观视角探索肿瘤发生发展的过程中涌现了许多对临床决策有价值的信息载体,循环肿瘤DNA(circulating tumor DNA, ctDNA)就是其中之一。在肿瘤发展的不同阶段,ctDNA展现出了包括评估疗效、预测预后、监测复发等在内的多种诊疗价值。本文主要阐述ctDNA在非小细胞肺癌临床诊疗不同时期的应用研究进展。 相似文献
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随着二代测序技术的发展,循环肿瘤DNA(circulating tumor DNA,ctDNA)检测在乳腺癌中的应用得到越来越多的关注。目前国内外大量研究显示ctDNA检测技术在监测肿瘤负荷、疗效预测、早期诊断、预后分析等方面具有广阔的应用价值。在乳腺癌诊疗走向个体化精准的时代,ctDNA检测能够为患者提供更为精准的诊断,指导临床治疗。 相似文献
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《中华乳腺病杂志(电子版)》2017,(3)
在乳腺癌发展过程中,肿瘤细胞内的DNA片段可进入血液循环,形成细胞游离DNA(cfDNA)。随着肿瘤研究的发展以及诊断技术的进步,cfDNA尤其是循环肿瘤DNA(ctDNA)检测在肿瘤的早期诊断、病情评估、药物反应监测、复发转移及预后的预测等方面均有着重要的应用价值,有望成为新一代的乳腺癌诊断新方法。笔者就cfDNA的生成机制以及乳腺癌中有关cfDNA/ctDNA的研究内容作一综述。 相似文献
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乳腺癌已进入分子分型指导下的个体化诊疗时代,但是诊治过程中的检测手段仍以组织活检、影像学检查及传统的蛋白标志物检测为主,无法及时为临床医师提供准确、全面、动态的肿瘤学信息。循环肿瘤DNA(circulating tumor DNA,ctDNA)作为新兴的“液体活检”之一,其检测结果能为乳腺癌的早期诊断、分子分型、疗效评估及复发监测提供重要信息,显示了良好的临床应用前景。本文就ctDNA在乳腺癌临床诊治中的研究进展进行综述。 相似文献
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乳腺癌在中国的发病率和病死率呈逐渐上升的趋势,因此,对乳腺癌的早期诊断、预测复发以及延长患者的生存期至关重要。活体组织检查作为一种侵入性的操作并非总是可行的,影像学检查和肿瘤标志物检测均无法提供足够的肿瘤特征信息以指导进一步的治疗。因此,近年来,液体活体组织检查已经逐渐取代肿瘤活体组织检查。循环肿瘤DNA(ctDNA)存在于肿瘤患者的血液循环中,在血浆游离的DNA中,ctDNA所占的比例极小,因此,ctDNA的检测成为一项难题。基因测序技术的发展使DNA的定性和定量检测成为可能,对肿瘤患者的ctDNA进行基因分析受到越来越多的关注。ctDNA因其具有侵害性小、简便易行等优点而成为一种新型的循环肿瘤标志物,ctDNA检测也成为了目前最重要的液体活体组织检查手段,在乳腺癌的精准治疗领域具有广阔的应用前景,可用于乳腺癌的早期诊断、监测疗效、探索耐药机制、预测疾病复发和判断预后等诸多方面,可为乳腺癌治疗方法的选择提供有利的依据,为乳腺癌更加精准化的治疗提供契机,从而真正实现乳腺癌患者的个体化治疗。 相似文献
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循环肿瘤DNA(ctDNA)是肿瘤细胞通过坏死、凋亡或直接分泌的方式向血液中释放的游离DNA。ctDNA常携带肿瘤相关的单核苷酸变异、拷贝数改变及结构变异等遗传学改变,这一特点促使循环肿瘤DNA成为潜在的生物标记物。以聚合酶链式反应(PCR)或二代测序(NGS)为基础的检测技术的进步提高了ctDNA检测的敏感性和信息量。ctDNA作为一种“液体活检”方法因其简便易行、侵害性小、实时动态佳等优势在乳腺癌领域得到了广泛研究,可以协助早期诊断、监测疗效、探索耐药机制、预测疾病复发和判断预后,为确定肿瘤患者治疗策略提供依据,从而真正实现乳腺癌的个体化治疗。 相似文献
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Paola Carpinetti Elisa Donnard Fabiana Bettoni Paula Asprino Fernanda Koyama Andrei Rozanski Jorge Sabbaga Angelita Habr-Gama Raphael B. Parmigiani Pedro A.F. Galante Rodrigo O. Perez Anamaria A. Camargo 《Oncotarget》2015,6(35):38360-38371
Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice. 相似文献
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《Annals of oncology》2017,28(8):1996-2001
BackgroundRecent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB.Patients and methodsThis prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria.ResultsctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5–41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5–94.9, P = 0.004).ConclusionThis proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs. 相似文献
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Erina Takai Wataru Omata Yasushi Totoki Hiromi Nakamura Satoshi Shiba Akira Takahashi Kenjiro Namikawa Taisuke Mori Naoya Yamazaki Tatsuhiro Shibata Shinichi Yachida 《Cancer science》2021,112(11):4748-4757
Assessment of treatment efficacy of immune checkpoint inhibitors in melanoma patients is difficult as the response to these therapies varies among patients or lesions. The clonal evolution of cancer during immune checkpoint blockade therapy could cause treatment resistance. We investigated the potential of liquid biopsy in monitoring the mutational profiles of metastatic melanoma during immunotherapy. Plasma samples collected from 21 Japanese metastatic melanoma patients before immune checkpoint blockade therapy were subjected to whole-exome sequencing (WES). Furthermore, 14 Japanese patients with melanoma were enrolled for longitudinal analysis of circulating tumor DNA (ctDNA). Plasma samples were collected prospectively before and during therapy and sequenced. WES of the pretreatment plasma from Japanese melanoma patients showed detectable ctDNA levels with wide ranges of variant allele frequencies within a sample, suggesting clonal and subclonal mutations in ctDNA. In targeted sequencing using longitudinal samples, ctDNA levels correlated with increased tumor size, while ctDNA content immediately decreased after a surge in a patient exhibiting pseudo-progression, suggesting the potential of ctDNA analysis in discriminating between pseudo- and true progression. Mutant ctDNA levels showed different patterns within the clinical course of specific patients, suggesting that these mutations were derived from different tumor clones with distinct therapeutic responses. During further investigation, WES of plasma samples from 1 patient showed marked differences in the mutational profiles of ctDNA, including expansive tumor evolution during an acute exacerbation. Immunotherapy may induce characteristic clonal evolutions of tumors; longitudinal analysis of ctDNA has the potential of determining these tumor evolution patterns and therapeutic responses. 相似文献
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Current classification and treatment of lung cancer rely increasingly on molecular and genetic testing. Obtaining tumor tissue is not always feasible and multiple biopsies are undesirable. In response to the demand for non-invasive molecular and genetic testing in cancer care, several liquid biopsy technologies, including circulating DNA (ctDNA), have been developed. ctDNA analysis is now technically feasible to be carried out in large scales and integrated into clinical practice owing to the advances in technology. Despite the challenges in improving test accuracy and cost-effectiveness, there are huge potentials for ctDNA analysis in lung cancer management. This review focuses on the clinical utility of ctDNA analysis in lung cancer, including early detection, monitoring treatment response and detecting residual disease, identification of genetic determinants for targeted therapy, and predicting efficacy of immune checkpoint blockade. 相似文献
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Hiroya Taniguchi Yoshiaki Nakamura Daisuke Kotani Hiroki Yukami Saori Mishima Kentaro Sawada Hiromichi Shirasu Hiromichi Ebi Takeharu Yamanaka Alexey Aleshin Paul R. Billings Matthew Rabinowitz Eiji Oki Ichiro Takemasa Takeshi Kato Masaki Mori Takayuki Yoshino 《Cancer science》2021,112(7):2915-2920
Adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival in patients with resected colorectal cancer. Potential utility of circulating tumor DNA (ctDNA) prior to and post surgery has been reported across various solid tumors. We initiated a new type of adaptive platform trials to evaluate the clinical benefits of ctDNA analysis and refine precision adjuvant therapy for resectable colorectal cancer, named CIRCULATE-Japan including three clinical trials. The GALAXY study is a prospectively conducted large-scale registry designed to monitor ctDNA for patients with clinical stage II to IV or recurrent colorectal cancer who can undergo complete surgical resection. The VEGA trial is a randomized phase III study designed to test whether postoperative surgery alone is noninferior to the standard therapy with capecitabine plus oxaliplatin for 3 months in patients with high-risk stage II or low-risk stage III colon cancer if ctDNA status is negative at week 4 after curative surgery in the GALAXY study. The ALTAIR trial is a double-blind, phase III study designed to establish the superiority of trifluridine/tipiracil as compared with placebo in patients with resected colorectal cancer who show circulating tumor–positive status in the GALAXY study. Therefore, CIRCULATE-Japan encompasses both “de-escalation” and “escalation” trials for ctDNA-negative and -positive patients, respectively, and helps to answer whether measuring ctDNA postoperatively has prognostic and/or predictive value. Our ctDNA-guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy. Analysis of ctDNA status could be utilized as a predictor of risk stratification for recurrence and to monitor the effectiveness of adjuvant chemotherapy. ctDNA is a promising, noninvasive tumor biomarker that can aid in tumor monitoring throughout disease management. 相似文献
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Xin Yi Jianhui Ma Yanfang Guan Rongrong Chen Ling Yang Xuefeng Xia 《International journal of cancer. Journal international du cancer》2017,140(12):2642-2647
For many decades it has been known that tumor DNA is shed into the blood. As a consequence of technological limitations, researchers were unable to comprehensively characterize circulating DNA. The advent of ultrasensitive and highly specific molecular assays has provided a comprehensive profile of the molecular characteristics and dynamics of circulating DNA in healthy subjects and cancer patients. With these new tools in hand, significant interest has been provoked for an innovative type of tumor biopsy termed a “liquid biopsy”. Liquid biopsies are obtained by minimal invasive blood draws from cancer patients. Circulating cancer cells, exosomes and a variety of molecules contained within the liquid biopsy including cell‐free circulating tumor DNA (ctDNA) can serve as promising tools to track cancer evolution. Attractive features of ctDNA are that ctDNA isolation is straightforward, ctDNA levels increase or decrease in response to the degree of tumor burden and ctDNA contains DNA mutations found in both primary and metastatic lesions. Consequently, the analysis of circulating DNA for cancer‐specific mutations might prove to be a valuable tool for cancer detection. Moreover, the capacity to screen for ctDNA in serial liquid biopsies offers the possibility to monitor tumor progression and responses to therapy and to influence treatment decisions that ultimately may improve patient survival. Here we focus on mutation detection in ctDNA and provide an overview of the characteristics of ctDNA, detection methods for ctDNA and the feasibility of ctDNA to monitor tumor dynamics. Current challenges associate with ctDNA will also be discussed. 相似文献
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基于循环肿瘤细胞(Circulating tumor cells,CTCs)和游离核酸的液体活检技术,在恶性肿瘤的诊断到随访的整个过程中都有潜在的应用价值。与传统组织活检相比,循环肿瘤DNA(Circulating tumor DNA,ctDNA)检测的优势在于风险小,可以进行连续检测,可以监测疾病的复发和随着时间推移对治疗的反应。ctDNA检测的灵敏度取决于使用的检测技术和遗传平台,还受肿瘤部位、分期、肿瘤异质性、肿瘤克隆性等的影响。ctDNA在肾细胞癌(Renal cell carcinoma,RCC)的治疗选择、耐药监测、对依维莫司的治疗反应预测等方面也得到很好的应用。本文主要对ctDNA在肾癌中的研究现状及挑战进行综述。 相似文献
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免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的抗实体瘤作用在部分肿瘤中逐渐被肯定,已进行临床应用,但是评估其疗效的生物标志物由于受到肿瘤空间和时间异质性的限制而无法满足临床需求。因此,有必要对治疗效果进行实时动态监测,从而了解肿瘤的基因突变、转移和复发以及对治疗的反应。通过液体活检分析到的循环肿瘤细胞(circulating tumor cells,CTCs)和循环肿瘤DNA(circulating tumor DNA,ctDNA)因为成功躲避了肿瘤异质性的识别而有望成为预测肿瘤免疫治疗效果的候选标志物。本文就CTCs和ctDNA在肿瘤免疫治疗中的应用进行综述,以期为临床医生选择合理有效的预测性生物标志物指标提供理论支持。 相似文献