Cornering metastases: therapeutic targeting of circulating tumor cells and stem cells

Faltas, Bishoy

doi:10.3389/fonc.2012.00068

Cited by 44 publications

(40 citation statements)

References 46 publications

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“…They can be broadly divided into invasive and non-invasive devices. The first ones include various vascular devices that allow continuous screening of CTCs and/or their elimination [121,122]. For instance, a vascular microtube device coated with halloysite and liposomes and containing doxorubicin, ethylene glycol, and E-selectin has been proposed.…”

Section: Elimination Of Ctcsmentioning

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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Section: Elimination Of Ctcsmentioning

confidence: 99%

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

Menyailo

Tretyakova

Denisov

2020

IJMS

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“…[7][8][9][10] The main treatments of metastatic cancer continue to use conventional methods such as chemotherapy. [7][8][9][10] The main treatments of metastatic cancer continue to use conventional methods such as chemotherapy.…”

Section: Doi: 101002/adtp201800112mentioning

confidence: 99%

“…However, only recently have studies focused on the importance of treatment of CTCs. [7][8][9][10] The main treatments of metastatic cancer continue to use conventional methods such as chemotherapy. In some cancer treatments, as in breast cancer, chemotherapy drugs for primary and metastatic cancer overlap.…”

Section: Doi: 101002/adtp201800112mentioning

confidence: 99%

Fluid Shear Stress Induces Drug Resistance to Doxorubicin and Paclitaxel in the Breast Cancer Cell Line MCF7

Triantafillu

Park

Kim

2018

Advanced Therapeutics

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Circulating tumor cells (CTCs) are known to have cancer stem cell (CSC) properties and survive physiological conditions of fluid shear stress (FSS). However, current chemotherapy screening techniques do not adequately recapitulate this FSS environment and are not predictive of a drug response. In this study, MCF7 and MDA-MB-231 cells under FSS are used as an in vitro model of CTCs. The effects of doxorubicin (DOX) and paclitaxel on sheared cells using WST8 assay and stemness (CD44 + /CD24 − ) and apoptosis (Annexin V + /7-AAD + ) using flow cytometry are tested. Quantitative polymerase chain reaction is used to test gene expression. It is shown that suspension-cultured and FSS treated MCF7 cells increase in drug resistance, especially with DOX. There is a synergistic increase in the CD44 + /CD24 − CSC-like population and an increase in drug resistance-related gene expression in MCF7 cells co-treated with FSS and drugs. There is also a correlated increase in STAT3 and NANOG expression under FSS. To the best of the authors' knowledge, this is the first report to suggest that the increase in CSC-like cells from FSS contributes to drug resistance via the STAT3/NANOG pathway.This increase in CTC drug resistance also highlights the importance of implementing FSS, which is unavailable in current drug screening techniques.

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“…Isolation and analysis of CTCs is important to improve understanding of their nature, and their ability to initiate metastases, and for effective development of next-generation cancer therapeutics [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Circulating tumor-cell detection and capture using microfluidic devices

Hajba

Guttman

2014

TrAC Trends in Analytical Chemistry

115

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A B S T R A C TCirculating tumor cells (CTCs) in the bloodstream are considered good indicators of the presence of a primary tumor or even metastases. CTC capture has great importance in early detection of cancer, especially in identifying novel therapeutic routes for cancer patients by finding personalized druggable targets for the pharmaceutical industry. Recent developments in microfluidics and nanotechnology improved the capabilities of CTC detection and capture, including purity, selectivity and throughput. This article covers the recent technological improvements in microfluidics-based CTC-capture methods utilizing the physical and biochemical properties of CTCs. We critically review the most promising hydrodynamic, dielectrophoretic and magnetic force-based microfluidic CTC-capture devices.

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Cornering metastases: therapeutic targeting of circulating tumor cells and stem cells

Cited by 44 publications

References 46 publications

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

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

Fluid Shear Stress Induces Drug Resistance to Doxorubicin and Paclitaxel in the Breast Cancer Cell Line MCF7

Circulating tumor-cell detection and capture using microfluidic devices

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