液体活检在肺癌精准医疗中的应用

肺癌是目前世界范围内最常见的恶性肿瘤之一,同时也是发病率最高、死亡率最高、增长速度最快且预后最差 的恶性肿瘤之一。许多国家都报道肺癌的发病率和死亡率均明显增高,男性肺癌发病率和死亡率均占所有恶性肿瘤的第一位,女性发病率占第二位,死亡率占第二位。近十余年来,液体活检由于其具有创伤性小、费用低、敏感性高等优点,逐渐成为了肺癌精准医疗中的研究热点。目前液体活检在肺癌精准医疗中的应用主要包括CTCs、ctDNA和外泌体等的检测。其中,CTCs不仅是肺癌早期诊断的有效手段、对肺癌的分期有一定帮助,还可作为疾病潜在的预后指标;ctDNA不仅可以作为肺癌诊断的可行工具、个性化治疗的参考指标,还可作为肿瘤潜在的生物标志物,帮助预测患者术后的复发;而外泌体被广泛认为是血液中潜在的肿瘤生物标志物,对肺癌的早期诊断、治疗及预后判断极其重要,甚至可以作为肺癌治疗的潜在靶点。本文基于不同的液体活检生物标记物,就CTCs、ctDNA、外泌体的生物学特性及临床应用进行了综述。     

肺癌液体活检研究进展

液体活检在恶性肿瘤的应用已经取得极大的进展,针对肺癌患者外周血中的循环肿瘤细胞(circulating tumor cells,CTCs)、循环肿瘤DNA(circulating tumor DNA,ctDNA)和外泌体fexosomes)的检测可以实时、有效地用于肺癌早期诊断、疗效监测、预后评估和精准治疗等方面.全文就CTCs、ctDNA和外泌体在肺癌领域的研究进展及临床使用的优势和潜在的应用价值进行综述,以期促进液体活检的应用,提高肺癌的临床疗效.     

液体活检和肿瘤精准医疗

精准医疗新技术——液体活检,既有极高的科研价值,又具备助力推进精准医疗临床实践的巨大潜能.它可用于癌症早期筛查、诊断、监控、治疗方案指导和疗效评估等众多领域,液体活检的优势使其成为最具发展潜力的肿瘤诊疗手段.本文围绕液体活检在临床肿瘤精准医疗的应用前景,从概念、特点、研究方法和个体化肿瘤治疗、临床应用及研究现状等方面进行阐述,展示了液体活检巨大的临床应用价值和市场前景.     

液体活检在结直肠癌领域的研究及应用现状

近年来,液体活检作为新兴的分子诊断技术,具有实时性和可重复性,在临床工作中发挥越来越重要的作用。液体活检主要通过无创方法收集患者体液,检测分析循环肿瘤细胞、循环肿瘤DNA、外泌体等生物学标志物。本文将从液体活检的生物学基础及其在结直肠癌临床应用方面进行综述。     

2023年度液体活检标志物研究进展年终盘点

液体活检技术作为新兴的检测技术,可以非侵入性地反映体内肿瘤的状态,在肿瘤筛检中具有广阔的应用前景。液体活检来源涵盖了不同类型的肿瘤相关物质,包括循环肿瘤DNA、循环肿瘤细胞、细胞外囊泡、非编码RNA等。本文就2023年度液体活检标志物检测及其在肿瘤的早期诊断、疗效评估、预后和复发转移监测等方面的研究新进展进行盘点,为深入探索以液体活检标志物为核心的肿瘤个体化诊治策略提供依据。     

液体活检在乳腺癌精准治疗中的应用进展及展望

在全球范围内,乳腺癌是女性最常见的恶性肿瘤。近年来,迅速扩大的基因组学知识体系不仅揭示了恶性肿瘤的复杂性,也使得恶性肿瘤的治疗范式从以肿瘤类型为导向逐渐转向以基因为导向,根据生物标志物分析为患者进行个体化治疗。目前大量研究已证实从患者获得肿瘤分子图谱优化了癌症个性化治疗方案的选择,以及对治疗反应、耐药及肿瘤复发的监测。而液体活检,通过对体液中肿瘤衍生材料所包含的基因组等数据进行分析,可以获得关于个体患者肿瘤特征的详细信息,为基于精准医学的治疗开辟新思路。在乳腺癌精准治疗中,液体活检可以预测生存预后、检测微小残留疾病(minimal residual disease,MRD)、监测治疗效果,在(新)辅助治疗及解救治疗中发挥作用。虽然液体活检在乳腺癌精准治疗方面的研究取得了令人瞩目的进展,但是仍存在一些问题,还需要更多的工作来进一步改进技术。本文将就近年来液体活检在乳腺癌精准治疗中的应用研究进展进行综述,并对未来的发展趋势予以展望。     

液体活检在子宫内膜癌中的应用

子宫内膜癌是常见的女性生殖系统恶性肿瘤之一.大多数子宫内膜癌可以早期诊断,预后良好,但是晚期和复发性子宫内膜癌预后不佳.液体活检作为无侵袭性的肿瘤标本获取方式,具有无创和可重复获取等优点,目前已经批准应用于多种恶性肿瘤的诊治过程.目前液体活检在子宫内膜癌的早期诊断、风险分层、治疗选择和实时疾病监测等方面也有相关的研究和...     

液体活检及其在非小细胞肺癌诊治中的研究进展

随着近几年科学技术的进步,液体活检技术也有了长足的发展,并在肿瘤的早期诊断及后期治疗中扮演着越来越重要的角色。相比于传统的组织活检,液体活检以其独有的无创性、便捷性、高重复性等特点在临床上得到更多的青睐,在未来有着巨大的发展潜力。本文重点探讨了循环肿瘤细胞（circulating tumor cells, CTCs）和循环肿瘤DNA（circulating tumor DNA, ctDNA）,作为液体活检最重要的两个检测对象,其历史、生物学特性,检测手段,局限性及其在非小细胞肺癌诊治中的应用。     

液体活检在非小细胞肺癌中的应用

随着精准医疗和个体化治疗在肺癌领域中的发展,对肿瘤分子生物学特性进行实时监测的要求越来越高。“液体活检”以其标本获取简便、创伤小、重复性高的特点在近年来引起了广泛关注。在所有肺癌患者中,非小细胞肺癌（ non small cell lung cancer,NSCLC）占85%~90%,针对NSCLC,特别是肺腺癌驱动突变的发现及相应靶向治疗的成功应用极大地改写了肺癌治疗的篇章,与此同时也对NSCLC相关分子生物学标志物的实时检测提出了更高的要求。本文以液体活检标志物的检测为起点,就其在NSCLC患者中的临床应用做一综述。     

液态活检在胃癌诊治中应用的研究进展

作为一种新兴的非侵入式病理检测技术，“液态活检”主要包括循环肿瘤细胞、循环肿瘤DNA、微小RNA以及外泌体等生物标志物的无创检测，随着精准医学的发展，其在肿瘤早期诊断、监测疾病进展以及疗效评价等方面显示出丰富的应用价值。胃癌是我国常见的恶性肿瘤之一，发病率居消化系统肿瘤之首。临床诊治过程中，胃癌的早期诊断、疗效监测、疾病复发转移预警等方面仍存在困境，液态活检为我们在该领域提供了新的手段和方法，具有广阔的临床应用前景。本文就液态活检在胃癌诊治中应用的最新研究进展做一综述。     

液体活检在非小细胞肺癌靶向治疗中应用

目的液体活检技术在肿瘤的检测方法中是尤为重要的检测手段。其在指导非小细胞肺癌(non-small cell lung cancer,NSCLC)靶向药物的选择、耐药监测以及预后评估等方面具有重要作用,本研究分析近年来国内外液体活检在NSCLC靶向治疗中的应用,以期明确液体活检对NSCLC靶向治疗的指导作用,进而有助于指导靶向药物在NSCLC治疗中的应用。方法应用PubMed、中国知网及中国期刊全文数据库检索系统,以"液体活检、循环肿瘤DNA、循环肿瘤细胞、靶向治疗、非小细胞肺癌"为关键词,检索2009-2019年发表的相关文献。纳入标准:(1)液体活检的机制;(2)靶向治疗在NSCLC中的应用;(3)NSCLC的治疗。排除标准:(1)中文非核心期刊的文献和英文非SCI收录文献;(2)结果重复且相对陈旧的实验研究。根据纳入标准和排除标准,最终29篇文献纳入分析。结果液体活检技术可对NSCLC的诊断、治疗及预后评估进行实时动态监测,及时获取肿瘤基因突变信息,在指导靶向药物选择,对耐药监测以及预后评估等方面具有重要作用。结论液体活检对指导NSCLC患者的靶向治疗具有重要作用,有助于NSCLC患者靶向药物治疗的选择。     

Serial monitoring of genomic alterations in circulating tumor cells of ER‐positive/HER2‐negative advanced breast cancer: feasibility of precision oncology biomarker detection

Nearly all estrogen receptor (ER)‐positive (POS) metastatic breast cancers become refractory to endocrine (ET) and other therapies, leading to lethal disease presumably due to evolving genomic alterations. Timely monitoring of the molecular events associated with response/progression by serial tissue biopsies is logistically difficult. Use of liquid biopsies, including circulating tumor cells (CTC) and circulating tumor DNA (ctDNA), might provide highly informative, yet easily obtainable, evidence for better precision oncology care. Although ctDNA profiling has been well investigated, the CTC precision oncology genomic landscape and the advantages it may offer over ctDNA in ER‐POS breast cancer remain largely unexplored. Whole‐blood (WB) specimens were collected at serial time points from patients with advanced ER‐POS/HER2‐negative (NEG) advanced breast cancer in a phase I trial of AZD9496, an oral selective ER degrader (SERD) ET. Individual CTC were isolated from WB using tandem CellSearch^®/DEPArray™ technologies and genomically profiled by targeted single‐cell DNA next‐generation sequencing (scNGS). High‐quality CTC (n = 123) from 12 patients profiled by scNGS showed 100% concordance with ctDNA detection of driver estrogen receptor α (ESR1) mutations. We developed a novel CTC‐based framework for precision medicine actionability reporting (MI‐CTCseq) that incorporates novel features, such as clonal predominance and zygosity of targetable alterations, both unambiguously identifiable in CTC compared to ctDNA. Thus, we nominated opportunities for targeted therapies in 73% of patients, directed at alterations in phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA), fibroblast growth factor receptor 2 (FGFR2), and KIT proto‐oncogene, receptor tyrosine kinase (KIT). Intrapatient, inter‐CTC genomic heterogeneity was observed, at times between time points, in subclonal alterations. Our analysis suggests that serial monitoring of the CTC genome is feasible and should enable real‐time tracking of tumor evolution during progression, permitting more combination precision medicine interventions.     

Liquid biopsy in central nervous system tumors: the potential roles of circulating miRNA and exosomes

The Central nervous system (CNS) tumor still remains the most lethal cancer, and It is hard to diagnose at an earlier stage on most occasions. It is found that recurrent disease is finally observed in patients who occurred chemo-resistance after completely primary treatment. It is a challenge that monitoring treatment efficacy and tumor recurrence of CNS tumors are full of risks and difficulties by brain biopsies. However, the brain biopsies are considered as an invasive technique with low specificity and low sensitivity. In contrast, the liquid biopsy is based on blood and cerebrospinal fluid (CSF) test, which is going to acceptable among the patients through it’s minimally invasive and serial bodily fluids. The advantages of liquid biopsy are to follow the development of tumors, provide new insights in real time, and accurate medical care. The major analytical constituents of liquid biopsy contain the Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating cell-free microRNAs (cfmiRNAs), and circulating exosomes. Liquid biopsy has been widely utilized in CNS tumors in recent years, and the CTCs and ctDNA have become the hot topics for researching. In this review, we are going to explain the clinical potential of liquid biopsy biomarkers in CNS tumor by testing circulating miRNAs and exosomes to evaluate diagnose, prognosis, and response to treatment.     

Single tube liquid biopsy for advanced non-small cell lung cancer

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM^high circulating tumor cells (CTC), EpCAM^low CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM^high CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM^low CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had ≥2 EpCAM^high CTC, 15% had ≥2 EpCAM^low CTC, 27% had ≥18 tdEV and 19% had ctDNA with ≥10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAM^high CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM^low CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.     

Analysis of colorectal cancer‐related mutations by liquid biopsy: Utility of circulating cell‐free DNA and circulating tumor cells

We recruited 56 colorectal cancer patients and compared the mutational spectrum of tumor tissue DNA, circulating cell‐free DNA (ccfDNA) and circulating tumor cell (CTC) DNA (ctcDNA) to evaluate the potential of liquid biopsy to detect heterogeneity of cancer. Tumor tissue DNA, ccfDNA, and ctcDNA were extracted from each patient and analyzed using next‐generation sequencing (NGS) and digital PCR. To maximize yields of CTC, three antibodies were used in the capture process. From 34 untreated patients, 53 mutations were detected in tumor tissue DNA using NGS. Forty‐seven mutations were detected in ccfDNA, including 20 not detected in tissues. Sixteen mutations were detected in ctcDNA, including five not detected in tissues. In 12 patients (35.3%), mutations not found in tumor tissues were detected by liquid biopsy: nine (26.5%) in ccfDNA only and three (8.8%) in ctcDNA only. Combination analysis of the two liquid biopsy samples increased the sensitivity to detect heterogeneity. From 22 stage IV patients with RAS mutations in their primary tumors, RAS mutations were detected in 14 (63.6%) ccfDNA and in eight (36.4%) ctcDNA using digital PCR. Mutations not detected in primary tumors can be identified in ccfDNA and in ctcDNA, indicating the potential of liquid biopsy in complementing gene analysis. Combination analysis improves sensitivity. Sensitivity to detect cancer‐specific mutations is higher in ccfDNA compared with ctcDNA.