Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medicine-Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Br J Cancer. 2022 Jul;127(2):173-184. doi: 10.1038/s41416-022-01768-9. Epub 2022 Mar 10.
Over the past decade, cancer diagnosis has expanded to include liquid biopsies in addition to tissue biopsies. Liquid biopsies can result in earlier and more accurate diagnosis and more effective monitoring of disease progression than tissue biopsies as samples can be collected frequently. Because of these advantages, liquid biopsies are now used extensively in clinical care. Liquid biopsy samples are analysed for circulating tumour cells (CTCs), cell-free DNA, RNA, proteins and exosomes. CTCs originate from the tumour, play crucial roles in metastasis and carry information on tumour heterogeneity. Multiple single-cell omics approaches allow the characterisation of the molecular makeup of CTCs. It has become evident that CTCs are robust biomarkers for predicting therapy response, clinical development of metastasis and disease progression. This review describes CTC biology, molecular heterogeneity within CTCs and the involvement of EMT in CTC dynamics. In addition, we describe the single-cell multi-omics technologies that have provided insights into the molecular features within therapy-resistant and metastasis-prone CTC populations. Functional studies coupled with integrated multi-omics analyses have the potential to identify therapies that can intervene the functions of CTCs.
在过去的十年中，癌症诊断除了组织活检外，还扩展到了液体活检。与组织活检相比，液体活检可以更早、更准确地诊断疾病，更有效地监测疾病进展，因为可以频繁采集样本。由于这些优势，液体活检现在在临床护理中得到了广泛应用。液体活检样本用于分析循环肿瘤细胞（CTC）、游离 DNA、RNA、蛋白质和外泌体。CTC 来源于肿瘤，在转移中起着至关重要的作用，并携带肿瘤异质性的信息。多种单细胞组学方法允许对 CTC 的分子组成进行特征描述。已经明显的是，CTC 是预测治疗反应、转移临床发展和疾病进展的强大生物标志物。这篇综述描述了 CTC 的生物学、CTC 内的分子异质性以及 EMT 在 CTC 动力学中的作用。此外，我们还描述了单细胞多组学技术，这些技术为了解治疗耐药和转移倾向的 CTC 群体的分子特征提供了线索。功能研究与集成的多组学分析相结合，有可能确定可以干预 CTC 功能的治疗方法。
