Molecular characterization and heterogeneity of circulating tumor cells in breast cancer

Jakabova, Anna; Bielčiková, Zuzana; Pospíšilová, Eliška; Matkowski, Rafał; Szynglarewicz, B.; Staszek-Szewczyk, Urszula; Zemanová, Milada; Petruželka, Luboš; Eliasova, Petra; Kološtová, Katarína; Bobek, Vladimír

doi:10.1007/s10549-017-4452-9

Cited by 30 publications

(22 citation statements)

References 17 publications

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“…Lots of studies have demonstrated the value of CTC quantification as a prognosis factor in metastatic as well as in metastatic patients [21,38]. However, recent studies underlined the high cellular heterogeneity within CTCs in breast [39][40][41][42][43], prostate [44][45][46][47], hepatocellular carcinoma [48], colorectal [49,50] [49] and in recent meta-analysis including 9 studies and 244 patients [56]. Similar discordance was observed at the epigenetic level [50].…”

Section: Isolation By Microfiltrationmentioning

confidence: 76%

Characterization of circulating tumor cells as a reflection of the tumor heterogeneity: myth or reality?

Brown

Gabriel

Cartron

et al. 2019

Drug Discovery Today

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Oncology has entered in the era of personalized medicine with its advantages such as limited invasiveness during sample collection, robustness, precision and speed. This new era has led to novel practices of tissue sampling (e.g. needle biopsy) and the main goal of diagnostic medicine is now to detect crucial events in "infinitely" small samples. The key question is now to determine if the rare cell events isolated and characterized from these samples are reliably reflecting the initial and/or metastatic disease and particularly the heterogeneity of the tumor. The present review will give a short overview of the most recent methods developed for the isolation and characterization of rare cell events in clinical practice with a specific focus on circulating tumor cells. We will discuss the biological value to study these cells at the single cell level and how these rare cell events can reflect tumor heterogeneity. The potential biomedical applications (disease modeling, drug screening, therapeutic decision, monitoring, etc.) will be critically discussed in light of precision medicine.

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Section: Isolation By Microfiltrationmentioning

confidence: 76%

Characterization of circulating tumor cells as a reflection of the tumor heterogeneity: myth or reality?

Brown

Gabriel

Cartron

et al. 2019

Drug Discovery Today

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“…It is very difficult to uncover their roles in tumor progression and metastasis as the very low frequencies in bone marrow or blood (Cristofanilli, 2006;Allard et al, 2014). An advantage is strong heterogeneity of CTCs is observed in cancer cell transition between mesenchymal and epithelial cell types (Yu et al, 2013;Jakabova et al, 2017). In addition, previous studies proved that the heterogeneity of biomarker expression are discordance between primary tumors and CTCs (Miyamoto et al, 2016).…”

Section: Single Cell Rna Sequencing For the Whole Transcriptome Analysismentioning

confidence: 99%

High-Throughput Transcriptome Profiling in Drug and Biomarker Discovery

et al. 2020

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The development of new drugs is multidisciplinary and systematic work. High-throughput techniques based on "-omics" have driven the discovery of biomarkers in diseases and therapeutic targets of drugs. A transcriptome is the complete set of all RNAs transcribed by certain tissues or cells at a specific stage of development or physiological condition. Transcriptome research can demonstrate gene functions and structures from the whole level and reveal the molecular mechanism of specific biological processes in diseases. Currently, gene expression microarray and high-throughput RNA-sequencing have been widely used in biological, medical, clinical, and drug research. The former has been applied in drug screening and biomarker detection of drugs due to its high throughput, fast detection speed, simple analysis, and relatively low price. With the further development of detection technology and the improvement of analytical methods, the detection flux of RNAseq is much higher but the price is lower, hence it has powerful advantages in detecting biomarkers and drug discovery. Compared with the traditional RNA-seq, scRNA-seq has higher accuracy and efficiency, especially the single-cell level of gene expression pattern analysis can provide more information for drug and biomarker discovery. Therefore, (sc) RNA-seq has broader application prospects, especially in the field of drug discovery. In this overview, we will review the application of these technologies in drug, especially in natural drug and biomarker discovery and development. Emerging applications of scRNA-seq and the third generation RNA-sequencing tools are also discussed.

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“…The number of CTCs changes during surgical and therapeutic interventions [20, [63][64][65]. Significant changes in the number of stem-and EMT-like CTC populations were observed in BC patients during neoadjuvant chemotherapy [64].…”

Section: Phenotypic Heterogeneitymentioning

confidence: 99%

Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds

Menyailo

Tretyakova

Denisov

2020

IJMS

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Metastasis being the main cause of breast cancer (BC) mortality represents the complex and multistage process. The entrance of tumor cells into the blood vessels and the appearance of circulating tumor cells (CTCs) seeding and colonizing distant tissues and organs are one of the key stages in the metastatic cascade. Like the primary tumor, CTCs are extremely heterogeneous and presented by clusters and individual cells which consist of phenotypically and genetically distinct subpopulations. However, among this diversity, only a small number of CTCs is able to survive in the bloodstream and to form metastases. The identification of the metastasis-initiating CTCs is believed to be a critical issue in developing therapeutic strategies against metastatic disease. In this review, we summarize the available literature addressing morphological, phenotypic and genetic heterogeneity of CTCs and the molecular makeup of specific subpopulations associated with BC metastasis. Special attention is paid to the need for in vitro and in vivo studies to confirm the tumorigenic and metastatic potential of metastasis-associating CTCs. Finally, we consider treatment approaches that could be effective to eradicate metastatic CTCs and to prevent metastasis. with partial EMT) and high metastatic potential [18,19]. In addition to the EMT features, CTCs can also exhibit stem-like characteristics, particularly self-renewal and multilineage differentiation ability [20].There is still no highly effective therapy for metastatic BC. Therapy targeted directly against CTCs seems to be promising. To date, various molecular markers of CTCs and their therapeutic targets that can be used to prevent cancer progression are known [21]. In addition, different therapeutic approaches for the elimination of CTCs have been proposed; however, none of them has been clinically approved. The reason is that the molecular and biological characteristics of the primary tumor and CTCs are not well understood. In our opinion, the main focus should be on the search for specific populations of CTCs responsible for the development of metastasis and the study of their molecular makeup. These cells could be the primary therapeutic target for preventing metastatic progression [22]. Recent advances in single-cell sequencing allow one to determine the population structure of CTCs and identify metastasis-initiating cells [23][24][25][26], while in vitro and in vivo studies provide data on their proliferative, apoptotic, invasive, and other phenotypes [27].Nowadays, despite a large number of studies on CTC heterogeneity and their metastatic potential, there are still no generally accepted and universal markers of CTCs prone to metastasis. In this review, we systematized the data on metastatic CTCs in terms of their morphological, phenotypic, and genetic heterogeneity in BC, as well as emphasized the importance of studying these cells in vitro and in vivo and developing therapeutic approaches for their elimination to prevent metastasis. CTC Heterogeneity and the Molecular Makeup...

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Molecular characterization and heterogeneity of circulating tumor cells in breast cancer

Cited by 30 publications

References 17 publications

Characterization of circulating tumor cells as a reflection of the tumor heterogeneity: myth or reality?

Characterization of circulating tumor cells as a reflection of the tumor heterogeneity: myth or reality?

High-Throughput Transcriptome Profiling in Drug and Biomarker Discovery

Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds

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