Janssen Ferdinand W, Lak Nathalie S M, Janda Claudia Y, Kester Lennart A, Meister Michael T, Merks Johannes H M, van den Heuvel-Eibrink Marry M, van Noesel Max M, Zsiros Jozsef, Tytgat Godelieve A M, Looijenga Leendert H J
Princess Máxima Center, Utrecht, the Netherlands.
Oncode Institute, Utrecht, the Netherlands.
NPJ Precis Oncol. 2024 Aug 3;8(1):172. doi: 10.1038/s41698-024-00657-z.
Liquid biopsies are emerging as an alternative source for pediatric cancer biomarkers with potential applications during all stages of patient care, from diagnosis to long-term follow-up. While developments within this field are reported, these mainly focus on dedicated items such as a specific liquid biopsy matrix, analyte, and/or single tumor type. To the best of our knowledge, a comprehensive overview is lacking. Here, we review the current state of liquid biopsy research for the most common non-central nervous system pediatric solid tumors. These include neuroblastoma, renal tumors, germ cell tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas, and liver tumors. Within this selection, we discuss the most important or recent studies involving liquid biopsy-based biomarkers, anticipated clinical applications, and the current challenges for success. Furthermore, we provide an overview of liquid biopsy-based biomarker publication output for each tumor type based on a comprehensive literature search between 1989 and 2023. Per study identified, we list the relevant liquid biopsy-based biomarkers, matrices (e.g., peripheral blood, bone marrow, or cerebrospinal fluid), analytes (e.g., circulating cell-free and tumor DNA, microRNAs, and circulating tumor cells), methods (e.g., digital droplet PCR and next-generation sequencing), the involved pediatric patient cohort, and proposed applications. As such, we identified 344 unique publications. Taken together, while the liquid biopsy field in pediatric oncology is still behind adult oncology, potentially relevant publications have increased over the last decade. Importantly, steps towards clinical implementation are rapidly gaining ground, notably through validation of liquid biopsy-based biomarkers in pediatric clinical trials.
液体活检正逐渐成为儿科癌症生物标志物的另一种来源，在从诊断到长期随访的患者护理各个阶段都有潜在应用。虽然该领域有相关进展报道，但主要集中在特定项目，如特定的液体活检基质、分析物和/或单一肿瘤类型。据我们所知，目前缺乏全面的综述。在此，我们回顾了针对最常见的非中枢神经系统儿科实体瘤的液体活检研究现状。这些肿瘤包括神经母细胞瘤、肾肿瘤、生殖细胞肿瘤、骨肉瘤、尤因肉瘤、横纹肌肉瘤和其他软组织肉瘤，以及肝肿瘤。在这个范围内，我们讨论了涉及基于液体活检的生物标志物的最重要或最新研究、预期的临床应用以及成功面临的当前挑战。此外，基于1989年至2023年间的全面文献搜索，我们概述了每种肿瘤类型基于液体活检的生物标志物发表情况。对于每一项确定的研究，我们列出了相关的基于液体活检的生物标志物、基质（如外周血、骨髓或脑脊液）、分析物（如循环游离和肿瘤DNA、微小RNA和循环肿瘤细胞）、方法（如数字液滴PCR和下一代测序）、涉及的儿科患者队列以及提出的应用。通过这种方式，我们确定了344篇独特的出版物。总体而言，虽然儿科肿瘤学中的液体活检领域仍落后于成人肿瘤学，但在过去十年中，潜在相关的出版物有所增加。重要的是，临床实施的步伐正在迅速推进，特别是通过在儿科临床试验中对基于液体活检的生物标志物进行验证。
