"Circulating Tumor Cells: Finding Rare Events for a Huge Knowledge of Cancer Dissemination".
Ontology highlight
ABSTRACT:
SUBMITTER: Alix-Panabieres C
PROVIDER: S-EPMC7140633 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
"Circulating Tumor Cells: Finding Rare Events for a Huge Knowledge of Cancer Dissemination".
Cells 20200309 3
Circulating tumor cells (CTCs) as real-time liquid biopsy [...]. ...[more]
Similar Datasets
Project description:Traditional factors currently used for prognostic stratification do not always adequately predict treatment response and disease evolution in advanced breast cancer patients. Therefore, the use of blood-based markers, such as circulating tumor cells (CTCs), represents a promising complementary strategy for disease monitoring. In this retrospective study, we explored the role of CTC counts as predictors of disease evolution in breast cancer patients with limited metastatic dissemination.A total of 492 advanced breast cancer patients who had a CTC count assessed by CellSearch prior to starting a new line of systemic therapy were eligible for this analysis. Using the threshold of 5 CTCs/7.5 ml of blood, pretreatment CTC counts were correlated in the overall population with metastatic site distribution, evaluated at baseline and at the time of treatment failure, using Fisher's exact test. Time to visceral progression and time to the development of new metastatic lesions and sites were estimated in patients with nonvisceral metastases and with single-site metastatic disease, respectively, by the Kaplan-Meier method. Survival times were compared between groups according to pretreatment CTC count by logrank test.In the overall population, a pretreatment level ?5 CTCs/7.5 ml was associated with an increased baseline number of metastatic sites compared with <5 CTCs/7.5 ml (P?=?0.0077). At the time of treatment failure, patients with ?5 CTCs/7.5 ml more frequently developed new metastatic lesions and sites compared with those with <5 CTCs/7.5 ml (development of new lesions: P?=?0.0002; development of new sites: P?=?0.0031). Among patients with disease originally confined to nonvisceral sites, ?5 CTCs/7.5 ml was associated with remarkably shorter time to visceral metastases (P?=?0.0021) and overall survival (P?=?0.0006) compared with <5 CTCs/7.5 ml. In patients with single-site metastatic disease, ?5 CTCs/7.5 ml was associated with a significant reduction of the time to development of new metastatic sites (P?=?0.0051) and new lesions (P?=?0.0002) and with worse overall survival (P?=?0.0101).Our results suggest that baseline CTC counts can be used as an early predictor of metastatic potential in breast cancer patients with limited metastatic dissemination.
| S-EPMC4303121 | biostudies-literature
Project description:BackgroundQuantification of circulating tumor cells (CTC) is valuable for evaluation of non-small cell lung cancer (NSCLC). The sensitivity of current methods constrains their use to detect rare CTCs in early stage. Here we evaluate a novel method, ligand-targeted polymerase chain reaction (LT-PCR), that can detect rare CTCs in NSCLC patients.MethodsCTCs were enriched by immunomagnetic depletion of leukocytes and then labeled by a conjugate of a tumor-specific ligand and an oligonucleotide. After washing off free conjugates, the bound conjugates were stripped from CTCs and then analyzed by qPCR. To evaluate the clinical utility, blood samples were obtained from 72 NSCLC patients (33 initially diagnosed and 39 on chemotherapy), 20 benign patients, and 24 healthy donors.ResultsExperiments with healthy blood spiked with tumor cells indicated the LT-PCR allows specific detection of CTC. The clinical study showed that the initially diagnosed patients have an average of 20.8 CTC units with metastatic diseases, 11.8 CTC units with localized diseases, and 6.0 CTC units with benign diseases. With the threshold of 8.5 CTC units, the assay can detect 80% of stage I/II, 67% of stage III, and 93% of stage IV cancer. With the benign patients and healthy donors as control group, the method can detect cancer with a sensitivity of 81.8% and a specificity of 93.2%.ConclusionThe LT-PCR would allow quantification of CTC in NSCLC patients at a more sensitive level, providing a potential tool for stratifying malignant lung diseases, especially at early stage.
| S-EPMC3855610 | biostudies-literature
Project description:Circulating tumor cells (CTCs) are shed into the bloodstream from primary and metastatic tumor deposits. Their isolation and analysis hold great promise for the early detection of invasive cancer and the management of advanced disease, but technological hurdles have limited their broad clinical utility. We describe an inertial focusing-enhanced microfluidic CTC capture platform, termed "CTC-iChip," that is capable of sorting rare CTCs from whole blood at 10(7) cells/s. Most importantly, the iChip is capable of isolating CTCs using strategies that are either dependent or independent of tumor membrane epitopes, and thus applicable to virtually all cancers. We specifically demonstrate the use of the iChip in an expanded set of both epithelial and nonepithelial cancers including lung, prostate, pancreas, breast, and melanoma. The sorting of CTCs as unfixed cells in solution allows for the application of high-quality clinically standardized morphological and immunohistochemical analyses, as well as RNA-based single-cell molecular characterization. The combination of an unbiased, broadly applicable, high-throughput, and automatable rare cell sorting technology with generally accepted molecular assays and cytology standards will enable the integration of CTC-based diagnostics into the clinical management of cancer.
| S-EPMC3760275 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy.
| S-EPMC5528974 | biostudies-other
Project description:Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of-evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC.
| S-EPMC5528978 | biostudies-literature
Project description:Isolation, release and culture of rare circulating tumor cells (CTCs) may, if implemented, promote the progress of individualized anti-tumor therapies. To realize the release of CTCs without disruption of their viability for further culture and analysis, we designed an effective photocontrolled CTC capture/release system by combination of photochemistry and immunomagnetic separation. 7-Aminocoumarin was synthesized as the phototrigger to bridge the connection between the anti-EpCAM antibody and the magnetic beads. The coumarin moieties produced cleavage of a C-O bond under both ultraviolet (UV) and near-infrared (NIR) light illumination, breaking the bridge and releasing CTCs from the immunomagnetic beads. Compared with conventional immunomagnetic separation systems, the negative influence of absorbed immunomagnetic beads on further CTCs culture and analysis was effectively eliminated. The system can specifically recognize 102 MCF-7 cells in 1 mL of human whole blood samples with 90% efficiency and 85% purity. Under the irradiation of UV and NIR light, 73 ± 4% and 52 ± 6% of captured cells were released with a viability of 90% and 97%, respectively. Furthermore, this technique has been used to detect CTCs from whole blood of cancer patients with high purity. This study demonstrates that the photochemical-based immunomagnetic separation method for isolating, releasing and culturing CTCs from clinic patients may provide new opportunities for cancer diagnosis and personalized therapy.
| S-EPMC5507187 | biostudies-literature
Project description:The clinical potential of circulating tumor cells (CTCs) in managing cancer metastasis is significant. However, low CTC isolation purities from patient blood have hindered sensitive molecular assays of these rare cells. Described herein is the ultra-pure isolation of CTCs from patient blood samples and how this platform has enabled highly specific molecular (mRNA and miRNA) profiling of patient CTCs.
| S-EPMC5039969 | biostudies-literature
Project description:Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years1,2. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study3, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.
| S-EPMC6986897 | biostudies-literature
Project description:The CellMax (CMx®) platform was developed to enrich for epithelial circulating tumor cells (CTCs) in the whole blood. This report provides assay performance data, including accuracy, linearity, limit of blank, limit of detection (LOD), specificity, and precision of enumeration of cancer cell line cells (CLCs) spiked in cell culture medium or healthy donor blood samples. Additionally, assay specificity was demonstrated in 32 young healthy donors and clinical feasibility was demonstrated in a cohort of 47 subjects consisting of healthy donors and patients who were colonoscopy verified to have colorectal cancer, adenomas, or a negative result. The CMx platform demonstrated high accuracy, linearity, and sensitivity for the enumeration of all CLC concentrations tested, including the extremely low range of 1 to 10 cells in 2 mL of blood, which is most relevant for early cancer detection. Theoretically, the assay LOD is 0.71 CTCs in 2 mL of blood. The analytical specificity was 100% demonstrated using 32 young healthy donor samples. We also demonstrated precision across multiple days and multiple operators, with good reproducibility of recovery efficiency. In a clinical feasibility study, the CMx platform identified 8 of 10 diseased subjects as positive (80% clinical sensitivity) and 4 of 5 controls as negative (80% clinical specificity). We also compared processing time and transportation effects for similar blood samples from two different sites and assessed an artificial intelligence-based counting method. Finally, unlike other platforms for which captured CTCs are retained on ferromagnetic beads or tethered to the slide surface, the CMx platform's unique airfoam-enabled release of CTCs allows captured cells to be transferred from a microfluidic chip to an Eppendorf tube, enabling a seamless transition to downstream applications such as genetic analyses and live cell manipulations.
| S-EPMC6939390 | biostudies-literature
Project description:Cancer cells that leave the primary tumor can seed metastases in distant organs, and it is thought that this is a unidirectional process. Here we show that circulating tumor cells (CTCs) can also colonize their tumors of origin, in a process that we call "tumor self-seeding." Self-seeding of breast cancer, colon cancer, and melanoma tumors in mice is preferentially mediated by aggressive CTCs, including those with bone, lung, or brain-metastatic tropism. We find that the tumor-derived cytokines IL-6 and IL-8 act as CTC attractants whereas MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 are mediators of CTC infiltration into mammary tumors. We show that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including the chemokine CXCL1. Tumor self-seeding could explain the relationships between anaplasia, tumor size, vascularity and prognosis, and local recurrence seeded by disseminated cells following ostensibly complete tumor excision.
| S-EPMC2810531 | biostudies-literature