Circulating Endothelial Cells and Their Subpopulations: Role as Predictive Biomarkers in Antiangiogenic Therapy for Colorectal Cancer

Manzoni, M.; Comolli, Giuditta; Torchio, Martina; Mazzini, Giuliano; Danova, Marco

doi:10.1016/j.clcc.2014.12.002

Cited by 26 publications

(13 citation statements)

References 53 publications

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“…These aspects, together with the heterogeneity of the patients series in the various studies, limit their potential to guide therapeutic strategies in clinical practice (69). In spite of these shortfalls, steps forward in the definition of the potential utility of CECs and EPCs for clinical purposes have been achieved, although reliable quantification of these cells is a work in progress and the interpretation of results must be made cautiously (35,10,70,71). In order to validate future reports that indicate, within well-designed trials, a true clinical value for both CECs and EPCs, unambiguous phenotypic definition of these cells together with careful inter-laboratory standardization of the quantitative techniques of analysis, including FCM, are mandatory.…”

Section: Discussionmentioning

confidence: 99%

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

Danova

Comolli

Manzoni

et al. 2016

Molecular and Clinical Oncology

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Abstract. Malignant tumors are characterized by uncontrolled cell growth and metastatic spread, with a pivotal importance of the phenomenon of angiogenesis. For this reason, research has focused on the development of agents targeting the vascular component of the tumor microenvironment and regulating the angiogenic switch. As a result, the therapeutic inhibition of angiogenesis has become an important component of anticancer treatment, however, its utility is partly limited by the lack of an established methodology to assess its efficacy in vivo. Circulating endothelial cells (CECs), which are rare in healthy subjects and significantly increased in different tumor types, represent a promising tool for monitoring the tumor clinical outcome and the treatment response. A cell population circulating into the blood also able to form endothelial colonies in vitro and to promote vasculogenesis is represented by endothelial progenitor cells (EPCs). The number of both of these cell types is extremely low and they cannot be identified using a single marker, therefore, in absence of a definite consensus on their phenotype, require discrimination using combinations of antigens. Multiparameter flow cytometry (FCM) is ideal for rapid processing of high numbers of cells per second and is commonly utilized to quantify CECs and EPCs, however, remains technically challenging since there is as yet no standardized protocol for the identification and enumeration of these rare events. Methodology in studies on CECs and/or EPCs as clinical biomarkers in oncology is heterogeneous and data have been obtained from different studies leading to conflicting conclusions. The present review presented a critical review of the issues that limit the comparability of results of the most significant studies employing FCM for CEC and/or EPC detection in patients with cancer.

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Section: Discussionmentioning

confidence: 99%

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

Danova

Comolli

Manzoni

et al. 2016

Molecular and Clinical Oncology

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“…Whether metastatic tumors may be more dependent on angiogenesis than micrometastases is one of the unsolved questions which might partially explain the failure of the anti-VEGF monoclonal antibody Bevacizumab in adjuvant setting [41]. The role of circulating endothelial cells as a potential biomarker of efficacy of antiangiogenic therapies has been widely investigated through CellSearch system, which reached a sufficient level of sensitivity for circulating endothelial cell quantification and monitoring during the course of the disease and in response to treatment [42]. Results from clinical trials investigating the predictive role of circulating endothelial cell in CRC patients treated with antiangiogenic therapies are conflicting and thus deserve further attention.…”

Section: Dapi 40xmentioning

confidence: 99%

The rationale for liquid biopsy in colorectal cancer: a focus on circulating tumor cells

Gazzaniga

Raimondi

Nicolazzo

et al. 2015

Expert Review of Molecular Diagnostics

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Capturing circulating tumor cells (CTCs) and/or circulating tumor DNA from blood, which represents a precious source of biological material derived from both primary and metastatic tumors, has been named a 'liquid biopsy'. While the circulating tumor DNA might be more representative of the bulk of the metastatic tumor, CTCs are thought to reflect more of the metastases-initiating cells. Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to track cancer evolution, as a fingerprint of the patient's individual tumor, and is easy to perform at every stage of the disease course, sounds attractive. This article mainly focuses on the applications of CTCs to track tumor dynamics in real time using colorectal cancer as a model system. The analysis of viable CTCs at DNA, RNA and protein levels, as well as their expansion in vitro, may allow deep investigation of the features of metastases-initiating cells.

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“…Although with a limited number of patients, we are the first group to demonstrate that by ISET it is possible to follow up patients under treatment with anti-angiogenic therapies. Other authors have demonstrated that the CellSearch ® System suffers a mask in CTC counts when patients receive those treatments 49–51. Probably, it happens because CTCs from patients who are treated with anti-angiogenic therapies lose their epithelial markers, the targets of CellSearch.…”

Section: Discussionmentioning

confidence: 99%

Early detection of poor outcome in patients with metastatic colorectal cancer: tumor kinetics evaluated by circulating tumor cells

Silva¹,

Chinen²,

Abdallah³

et al. 2016

OTT

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BackgroundColorectal cancer (CRC) is the third most prevalent cancer worldwide. New prognostic markers are needed to identify patients with poorer prognosis, and circulating tumor cells (CTCs) seem to be promising to accomplish this.Patients and methodsA prospective study was conducted by blood collection from patients with metastatic CRC (mCRC), three times, every 2 months in conjunction with image examinations for evaluation of therapeutic response. CTC isolation and counting were performed by Isolation by Size of Epithelial Tumor Cells (ISET).ResultsA total of 54 patients with mCRC with a mean age of 57.3 years (31–82 years) were included. Among all patients, 60% (n=32) were carriers of wild-type KRAS (WT KRAS) tumors and 90% of them (n=29) were exposed to monoclonal antibodies along with systemic treatment. Evaluating CTC kinetics, when we compared the baseline (pretreatment) CTC level (CTC1) with the level at first follow-up (CTC2), we observed that CTC1-positive patients (CTCs above the median), who became negative (CTCs below the median) had a favorable evolution (n=14), with a median progression-free survival (PFS) of 14.7 months. This was higher than that for patients with an unfavorable evolution (CTC1− that became CTC2+; n=13, 6.9 months; P=0.06). Patients with WT KRAS with favorable kinetics had higher PFS (14.7 months) in comparison to those with WT KRAS with unfavorable kinetics (9.4 months; P=0.02). Moreover, patients whose imaging studies showed radiological progression had an increased quantification of CTCs at CTC2 compared to those without progression (P=0.04).ConclusionThis study made possible the presentation of ISET as a feasible tool for evaluating CTC kinetics in patients with mCRC, which can be promising in their clinical evaluation.

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Circulating Endothelial Cells and Their Subpopulations: Role as Predictive Biomarkers in Antiangiogenic Therapy for Colorectal Cancer

Cited by 26 publications

References 53 publications

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

The rationale for liquid biopsy in colorectal cancer: a focus on circulating tumor cells

Early detection of poor outcome in patients with metastatic colorectal cancer: tumor kinetics evaluated by circulating tumor cells

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