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The major cause of cancer-associated mortality is tumor metastasis, a disease that is far from understood. Many studies have observed circulating tumor cells (CTCs) in patients' circulation systems, and a few latest investigations showed that CTC clusters have a potentially high capacity of metastasis. The capture and analysis of CTC clusters offer new insights into tumor metastasis and can facilitate the development of cancer treatments. We reviewed the research history of the CTC clusters, as well as the technologies used for detecting and isolating CTC clusters. In addition, we discuss the characteristics of CTC clusters and their roles in tumor dissemination. Clinical relevance of CTC clusters was also implicated in currently limited data. Moving forward, the next frontier in this field is to develop more efficient capture methods and decipher conundrums of characterization of CTC clusters. This will ultimately identify the clinical value of CTC clusters as a biomarker and therapeutic target.

Circulating tumor cells, a component of the “liquid biopsy”, hold great potential to transform the current landscape of cancer therapy. A key challenge to unlocking the clinical utility of CTCs lies in the ability to detect and isolate these rare cells using methods amenable to downstream characterization and other applications. In this review, we will provide an overview of current technologies used to detect and capture CTCs with brief insights into the workings of individual technologies. We focus on the strategies employed by different platforms and discuss the advantages of each. As our understanding of CTC biology matures, CTC technologies will need to evolve, and we discuss some of the present challenges facing the field in light of recent data encompassing epithelial-to-mesenchymal transition, tumor-initiating cells, and CTC clusters. •We present a comprehensive overview of CTC detection and capture technologies.•We provide a conceptual description of strategies used in different technologies.•We highlight the key features of individual technologies.•We discuss CTC technology performance in the context of clinical studies.

Circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) have been shown to correlate negatively with patient survival. Actual CTC counts before and after treatment can be used to aid in the prognosis of patient outcomes. The presence of circulating tumor materials (CTMat) can advertise the presence of metastasis before clinical presentation, enabling the early detection of relapse. Importantly, emerging evidence is indicating that cancer treatments can actually increase the incidence of CTCs and metastasis in pre-clinical models. Subsequently, the study of CTCs, their biology and function are of vital importance. Emerging technologies for the capture of CTC/CTMs and CTMat are elucidating vitally important biological and functional information that can lead to important alterations in how therapies are administered. This paves the way for the development of a “liquid biopsy” where treatment decisions can be informed by information gleaned from tumor cells and tumor cell debris in the blood.

Purpose Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors. Methods We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival. Results Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7–639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89–481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively. Conclusions CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

It has been proved that most of the deaths due to cancer are related to metastasis. This process occurs through the separation of cells from the primary tumor and maintenance in the circulation systems in the body. Finally, if the condition for the relocalizing of them in other sites becomes appropriate, they produce new tumors in various parts of the body. The number of these circulating tumor cells (CTCs) in the blood is very rare. So, detecting and counting them is difficult, but very vital. There are various techniques for the detection of CTCs, which along with them, nanomaterials are suitable tools for this purpose due to their small sizes and unique properties. Because of the high efficiency of these materials, it is possible to exceed the other mentioned methods. In this review, we aim to render a comprehensive study about recent advances in the capture and subsequent release of the CTCs using different types of nanomaterials.

Circulating tumor cell enrichment and enumeration are advancing early detection of cancer, monitoring of therapy response, and even next-generation therapies. Efficiently capturing rare cells from complex biological fluids is essential in both diagnostic and therapeutic applications. EpCAM-positive tumor cells are specifically captured by utilizing covalently immobilized anti-EpCAM monoclonal antibodies onto the surface of chemically modified glass microbeads. To maximize the capture efficiency, bead geometry, immobilization conditions, flow rate, and anticoagulant dosage were systematically optimized. An in vitro flow-capture system was designed and used to evaluate the capture efficiency of the proposed technology by utilizing HTC116 colon cancer cell-spiked model media. The effect of substrate surface pretreatment was characterized by goniometry, while the capture performance was monitored by flow cytometry and fluorescent microscopy. The specific capture ability of the bioactive microbead substrate reached over 130,000 cells in the laboratory-scale cartridge (V(cartridge) = 2.6 cm3; m(bead) = 4 g). This capture efficiency suggests a promising rare-cell capture utilization of the proposed technology and may be used for research, diagnostic, and therapeutic purposes. In this paper, we reported on the development and feasibility test of a high-performance bioactive glass-microbead cell capture substrate. Due to the relevance and novelty of the reported results, with further development, the versatile platform technology presented could be readily implemented to capture tumor cells from complex biological samples and represent an additional complementary tool to existing cancer diagnostics and therapies.

Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.

The detection and analysis of circulating tumor cells (CTCs) from patients´ blood is important to assess tumor status; however, it remains a challenge. In the present study, we developed a programmable DNA-responsive microchip for the highly efficient capture and nondestructive release of CTCs via nucleic acid hybridization. Transparent and patternable substrates with hierarchical architectures were integrated into the microchip with herringbone grooves, resulting in greatly enhanced cell-surface interaction via herringbone micromixers, more binding sites, and better matched topographical interactions. In combination with a high-affinity aptamer, target cancer cells were specifically and efficiently captured on the chip. Captured cancer cells were gently released from the chip under physiological conditions using toehold-mediated strand displacement, without any destructive factors for cells or substrates. More importantly, aptamer-containing DNA sequences on the surface of the retrieved cancer cells could be further amplified by polymerase chain reaction (PCR), facilitating the detection of cell surface biomarkers and characterization of the CTCs. Furthermore, this system was extensively applied to the capture and release of CTCs from patients´ blood samples, demonstrating a promising high-performance platform for CTC enrichment, release, and characterization.

Purpose To explore circulating tumor cell (CTCs) counts in different stages of prostate cancer (PC) in association with tumor burden, metastatic pattern and conventional serum biomarkers. Overall survival (OS) analyses were conducted with respect to optimized CTC cutoff levels. Methods Circulating tumor cell counts were assessed in healthy controls ( n  = 15) as well as in locally advanced high risk (LAPC, n  = 20), metastatic castration resistant (mCRPC, n  = 40) and taxane-refractory (mTRPC, n  = 15) PC patients. CTCs were detected using the CellSearch™ System. Results In metastatic PC (mPC), CTC counts were significantly increased compared to LAPC ( p  < 0.001). In LAPC, CTCs were at control level ( p  = 0.66). Patients with both bone and visceral lesions revealed the highest median CTC count ( p  = 0.004), whereas patients with sole soft tissue metastases displayed CTC counts comparable to controls ( p  = 0.16). No correlation was observed between CTC counts and osseous tumor burden assessed by bone lesion count ( p  = 0.54) or bone scan index ( p  = 0.81). CTC counts revealed a positive correlation with alkaline phosphatase ( p  < 0.001) and lactate dehydrogenase ( p  < 0.001) as well as a negative association with hemoglobin ( p  = 0.004) and PSA-doubling time ( p  = 0.01). Kaplan–Meier analyses demonstrated a cohort adjusted cutoff level of 3 CTCs with a shorter OS in case of ≥3 CTCs compared to <3 CTCs ( p  = 0.001), a cutoff level applicable in mCRPC ( p  = 0.003) but not in mTRPC patients ( p  = 0.054). Conclusions Circulating tumor cell counts are applicable as a prognostic molecular marker, especially in mCRPC patients harboring bone metastases with or without visceral metastases. For clinical practice, mPC patients with elevated CTC counts in combination with short PSA-DT, high alkaline phosphatase and lactate dehydrogenase levels as well as low hemoglobin levels are at high risk of disease progression and limited OS.

The highly efficient capture of circulating tumor cells (CTCs) in the blood is essential for the screening, treatment, and assessment of the risk of metastasis or recurrence of cancer. Immobilizing specific antibodies, such as EpCAM antibodies, on the material’s surface is currently the primary method for efficiently capturing CTCs. However, the strategies for immobilizing antibodies usually have the disadvantages of requiring multiple chemical reagents and a complex pre-treatment process. Herein we developed a simple strategy for the immobilization of EpCAM antibodies without additional chemical reagents. By utilizing the positive charge property of the photo-functionalized titanium dioxide (TiO 2 ), the negatively charged carboxyl terminal of EpCAM antibodies was immobilized by electrostatic interaction, allowing the antibodies to expose the antigen binding site fully. The experimental results showed that the photo-functionalized TiO 2 surface had a marked positive charge and super-hydrophilic properties that could immobilize large amounts of EpCAM antibodies and keep excellent activity. CTCs capture experiments in vitro showed that the EpCAM antibodies-modified photo-functionalized TiO 2 could efficiently capture CTCs. The results of blood circulation experiments in rabbits showed that the EpCAM antibodies-modified photo-functionalized TiO 2 could accurately capture CTCs from the whole body’s blood. It was foreseen that the strategy of simple immobilization of EpCAM antibodies based on photo-functionalized TiO 2 is expected to serve in the efficient capture of CTCs in the future.