Circulating tumor cells in precision oncology: clinical applications in liquid biopsy and 3D organoid model

Chang Yang,Wei-Lin Jin,Ge Lou,Bai-Rong Xia

doi:10.1186/s12935-019-1067-8

Chang Yang, Wei-Lin Jin + Show 2 more

Open Access

https://doi.org/10.1186/s12935-019-1067-8

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Abstract

Circulating tumor cells (CTCs) are a rare subset of cells found in the blood of patients with solid tumors, which function as a seed for metastases. Cancer cells metastasize through the bloodstream either as single migratory CTCs or as multicellular groupings—CTC clusters. The CTCs preserve primary tumor heterogeneity and mimic tumor properties, and may be considered as clinical biomarker, preclinical model, and therapeutic target. The potential clinical application of CTCs is being a component of liquid biopsy. CTCs are also good candidates for generating preclinical models, especially 3D organoid cultures, which could be applied in drug screening, disease modeling, genome editing, tumor immunity, and organoid biobanks. In this review, we summarize current knowledge on the value and promise of evolving CTC technologies and highlight cutting-edge research on CTCs in liquid biopsy, tumor metastasis, and organoid preclinical models. The study of CTCs offers broad pathways to develop new biomarkers for tumor patient diagnosis, prognosis, and response to therapy, as well as translational models accelerating oncologic drug development.

Highlights

Cancer incidence rate is stable in women and declining by approximately 2% per year in men, and cancer death rate in women and men declined annually by 1.4% and 1.8%, respectively, over the past decade [1], cancer remains the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018
As a seed for metastases, Circulating tumor cells (CTCs) conserve tumor heterogeneity and mimic tumor properties, allowing them to be applied to therapeutic targets and clinical biomarkers for disease screening, dynamic monitoring, and prognosis prediction
We focus on the clinical applications of CTCs, especially in liquid biopsy and 3D organoid model

Summary

Introduction

Cancer incidence rate is stable in women and declining by approximately 2% per year in men, and cancer death rate in women and men declined annually by 1.4% and 1.8%, respectively, over the past decade [1], cancer remains the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Dijkstra et al [77] have established and confirmed a platform that culture autologous tumor organoids together with peripheral blood lymphocytes to evaluate and stimulate tumor-specific T cell responses to epithelial cancers They have demonstrated that the value and novelty of this platform is to isolate tumor-reactive T cells and evaluate the therapeutic effect of T-cell-mediated attacks for the first time. The reduction of CTC clusters in mice blood with breast cancer led to a single increase in the number of circulating tumor cells, the total transfer in mice burden was reduced 80.7 times, 98.8% less than that in the control group, and prevented the formation of new metastases. Plakoglobin, keratin 14+, and CD44 are both involved in CTC aggregation, and whether they regulate tumor metastases in a separated or coordinated manner remains a question

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