Kuligina Ekaterina S, Yanus Grigoriy A, Imyanitov Evgeny N
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, 197758 St.-Petersburg, Russia.
Department of Medical Genetics, St.-Petersburg State Pediatric Medical University, 194100 St.-Petersburg, Russia.
Explor Target Antitumor Ther. 2025 Aug 8;6:1002333. doi: 10.37349/etat.2025.1002333. eCollection 2025.
Liquid biopsy (LB) is a complex of procedures aimed at the detection of tumor-derived fragments (nucleic acids, proteins, cells, etc.) persisting in the blood or other body fluids. It can be utilized for early cancer diagnosis, analysis of biomarkers of tumor drug sensitivity and prognosis, monitoring of minimal residual disease (MRD), etc. Circulating tumor DNA (ctDNA) is an accessible and reliable LB analyte as it may contain tumor-specific mutations and is amenable to efficient detection by next-generation sequencing (NGS) or droplet digital PCR (ddPCR). High level of ctDNA is typically associated with increased tumor burden and poor prognosis, whereas treatment-related ctDNA clearance increases the probability of a favorable disease outcome. Major efforts have been invested in enhancing the analytical performance of ctDNA detection. Stimulation of apoptosis of tumor cells by irradiation of cancer lumps has been shown to result in a transient but modest increase in ctDNA concentration. There are several sophisticated modifications of ultra-deep NGS protocols, which discriminate between "true" low-copy mutation-specific signals and sequencing artifacts. Slowing physiological ctDNA decay by interfering with liver macrophages and circulating nucleases has shown promise in animal experiments. Reproducibility of ctDNA-based LB assays remains insufficient for samples with ultra-low content of ctDNA; hence, interlaboratory harmonization of ctDNA testing procedures is of paramount importance.
液体活检（LB）是一系列旨在检测存在于血液或其他体液中的肿瘤衍生片段（核酸、蛋白质、细胞等）的程序。它可用于癌症早期诊断、肿瘤药物敏感性和预后生物标志物分析、微小残留病（MRD）监测等。循环肿瘤DNA（ctDNA）是一种易于获取且可靠的液体活检分析物，因为它可能包含肿瘤特异性突变，并且适合通过下一代测序（NGS）或数字液滴PCR（ddPCR）进行有效检测。ctDNA水平高通常与肿瘤负荷增加和预后不良相关，而与治疗相关的ctDNA清除则增加了疾病预后良好的可能性。人们已投入大量精力来提高ctDNA检测的分析性能。已证明通过照射癌块刺激肿瘤细胞凋亡会导致ctDNA浓度短暂但适度增加。超深度NGS方案有几种复杂的改进方法，可区分“真正的”低拷贝突变特异性信号和测序假象。通过干扰肝巨噬细胞和循环核酸酶来减缓生理性ctDNA衰变在动物实验中已显示出前景。对于ctDNA含量超低的样本，基于ctDNA的液体活检检测的重现性仍然不足；因此，ctDNA检测程序的实验室间协调至关重要。
