Role of circulating tumor cells and cancer stem cells in hepatocellular carcinoma

Nel, Ivonne; David, Paul; Gerken, Guido; Schlaak, J.F.; Hoffmann, Andreas-Claudius

doi:10.1007/s12072-014-9539-3

Cited by 18 publications

(17 citation statements)

References 42 publications

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“…Circulating tumor cells (CTC) are thought to be useful in individualizing and monitoring treatment in patients with solid tumors [ 1 , 2 ]. So far, CTC detection methods consist of enrichment and subsequent identification mostly with anti-cytokeratin (CK) or epithelial cell adhesion molecule (EpCAM) antibodies [ 3 ]. The epithelial-to-mesenchymal transition (EMT) can cause alteration of cellular features and loss of epithelial properties leading to a partial or complete switch to a mesenchymal phenotype.…”

Section: Introductionmentioning

confidence: 99%

Circulating Tumor Cell Composition in Renal Cell Carcinoma

Nel¹,

Gauler

Bublitz³

et al. 2016

PLoS ONE

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PurposeDue to their minimal-invasive yet potentially current character circulating tumor cells (CTC) might be useful as a “liquid biopsy” in solid tumors. However, successful application in metastatic renal cell carcinoma (mRCC) has been very limited so far. High plasticity and heterogeneity of CTC morphology challenges currently available enrichment and detection techniques with EpCAM as the usual surface marker being underrepresented in mRCC. We recently described a method that enables us to identify and characterize non-hematopoietic cells in the peripheral blood stream with varying characteristics and define CTC subgroups that distinctly associate to clinical parameters. With this pilot study we wanted to scrutinize feasibility of this approach and its potential usage in clinical studies.Experimental DesignPeripheral blood was drawn from 14 consecutive mRCC patients at the West German Cancer Center and CTC profiles were analyzed by Multi-Parameter Immunofluorescence Microscopy (MPIM). Additionally angiogenesis-related genes were measured by quantitative RT-PCR analysis.ResultsWe detected CTC with epithelial, mesenchymal, stem cell-like or mixed-cell characteristics at different time-points during anti-angiogenic therapy. The presence and quantity of N-cadherin-positive or CD133-positive CTC was associated with inferior PFS. There was an inverse correlation between high expression of HIF1A, VEGFA, VEGFR and FGFR and the presence of N-cadherin-positive and CD133-positive CTC.ConclusionsPatients with mRCC exhibit distinct CTC profiles that may implicate differences in therapeutic outcome. Prospective evaluation of phenotypic and genetic CTC profiling as prognostic and predictive biomarker in mRCC is warranted.

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Section: Introductionmentioning

confidence: 99%

Circulating Tumor Cell Composition in Renal Cell Carcinoma

Nel¹,

Gauler

Bublitz³

et al. 2016

PLoS ONE

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“…Many other studies in various types of cancer have come across with the similar conclusions, including breast, colorectal, gastric, liver, and NSCLC, etc. [120,123,[138][139][140][141][142][143][144][145].…”

Section: Cancer Migration Invasion Epithelial-mesenchymal Transitiomentioning

confidence: 99%

The Selection Strategy for Circulating Tumor Cells (CTCs) Isolation and Enumeration: Technical Features, Methods, and Clinical Applications

Hsieh¹,

Wu²

2016

Tumor Metastasis

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The key aim of the proposed chapter is to provide readers a brief description for the most important parts of the field of circulating tumor cells (CTCs): the core techniques, including negative and positive selection-based CTC isolation, and the differences between them. Most importantly, we will also review the clinical applications and important findings in clinical trials. The evidence-based review will not only help clinicians use CTCs to predict recurrence and foresee the disease-related outcomes but also to inspire the researchers in this field to conduct further investigations.

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“…An innovative methodology in CSC-targeted therapy is the siRNA-mediated downregulation of signaling pathways involved in carcinogenesis. Though CSC and CTC analysis may not be usable for treatment decisions at the moment, identifying and characterizing the individual tumor cell composition and the constitution of circulating non-hematopoietic cells in the blood of patients before therapy may add important information to the process of personalizing therapy [24]. …”

Section: Circulating Tumor or Cancer Stem Cellsmentioning

confidence: 99%

Hepatocellular Cancer: New Kids on the Block

Hoffmann

Gerken

2014

Gastrointest Tumors

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Background: With over 600,000 newly diagnosed hepatocellular cancer (HCC) patients worldwide every year and ongoing clinical research, it is surprising that many of the new molecular entities have not yet resulted in significant prolongation of progression-free or overall survival. Nevertheless, there are a number of promising agents currently under investigation. Given the unique tumor biology and heterogeneous clinical manifestations of HCC, the application of molecular and cellular markers could also benefit patient selection, disease prognosis and trial design. Summary: This paper provides an overview of the current therapeutic strategies for HCC in the curative and palliative settings. Furthermore, we introduce some of the promising small molecules and antibodies that may find their way into clinical practice, with a focus on substances that are currently in phase III testing. Finally, we summarize the role of promising biomarkers, such as circulating tumor or cancer stem cells. Key Message: Despite the rising prevalence of HCC and active clinical research, few therapeutic options besides sorafenib have been established. This review discusses the new therapeutic agents in the pipeline. Practical Implications: Although many promising preclinical studies have resulted in phase I-II trials on HCC, so far only the tyrosine and Raf kinase inhibitor sorafenib has made its way into the hands of physicians. This multikinase inhibitor is the only approved option for systemic treatment of advanced HCC. Currently, the development of promising approaches for disease management is guided by biomarkers such as molecular markers or cellular characteristics. The use of biomarkers may facilitate early diagnosis in high-risk groups and therefore enhance outcomes by detecting patients whose disease is still curable.

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Role of circulating tumor cells and cancer stem cells in hepatocellular carcinoma

Cited by 18 publications

References 42 publications

Circulating Tumor Cell Composition in Renal Cell Carcinoma

Circulating Tumor Cell Composition in Renal Cell Carcinoma

The Selection Strategy for Circulating Tumor Cells (CTCs) Isolation and Enumeration: Technical Features, Methods, and Clinical Applications

Hepatocellular Cancer: New Kids on the Block

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