The Role of Circulating Tumor Cells in Chemoresistant Metastatic Breast Cancer

Abstract

Breast cancer is the most frequent form of cancer among women and is one of the leading causes of death. Two routes of the metastatic process have been described: linear and parallel progression. A key factor is represented by circulating tumor cells (CTCs). CTCs detach from the primary tumor or develop from cancer stem cells (CSCs) that undergo epithelial-to-mesenchymal transition (EMT). CTCs migrate to the distant site where the reverse process occurs and a new tumor arises. One of the key problems of metastatic disease is chemoresistance, which leads to treatment failure and, eventually, death. The aim of this review is to present up-to-date data regarding the role of CTCs in chemoresistance in metastatic breast cancer (MBC) patients. A search in Cochrane Library and MEDLINE databases was performed. A total of 125 articles were identified. The results of the final 12 eligible studies revealed that CTCs having stem cell features and those with mesenchymal features are aggressive subtypes of cells that survive chemotherapy, being responsible for chemoresistance and thus for disease progression in MBC patients. The hemodynamic shear stress, alongside dynamic changes among CTCs during the disease, is also an important disease progression factor.

The Utilization of Optically Induced Dielectrophoresis (ODEP)-Based Cell Manipulation in a Microfluidic System for the Purification and Sorting of Circulating Tumor Cells (CTCs) with Different Sizes

“…In this work, the proposed ODEP microfluidic system was to (1) purify the CTCs from the remaining magnetic microbeads-bound blood cells, and (2) further sort and separate the CTCs with different sizes (Figure 2). Based on the operations, high-purity, label-free, and all possible CTCs with different size from a blood sample can be harvested, which is both biologically and clinically meaningful for the subsequent medical applications (e.g., prognosis evaluation of cancer [6,7], therapeutic response evaluation of cancer [8][9][10], or monitoring of cancer metastasis [11,12]) or fundamental studies (e.g., mechanisms behind cancer metastasis [15] or anti-cancer drug resistance [17,18]). This technical advantage is beyond what is possible by using other CTC isolation and purification methods by which the CTCs harvested are limited to certain CTC subtypes (e.g., EpCAM-positive CTCs [42]), are labeled with magnetic microbeads [42], or are in a low-purity manner (e.g., biophysicaland negative immunoselection-based CTC enrichment techniques [22,36]).…”

“…Therefore, the analysis of CTCs holds great promise for several clinical utilizations (e.g., cancer detection [4,5], prognosis evaluation of cancer [6,7], therapeutic response evaluation of cancer [8][9][10], or monitoring of cancer metastasis [11,12]). Compared with the clinical applications of CTCs simply based on the quantification of their cell number [6,11], the analysis of CTCs at molecular level (e.g., gene expression analysis) could pave a more promising route to Micromachines 2023, 14, 2170 2 of 17 comprehensively understand CTC heterogeneity [13,14], cancer progression [15,16], or mechanisms of therapeutic resistance [17,18]. To achieve this goal, the harvest of highpurity and all possible CTCs with different subtypes from the blood samples of cancer patients is crucially important.…”

Active Contours Driven by Cellular Neural Networks for Image Segmentation in Biomedical Application

“…A mention regarding the size of the clusters of cells found in the blood or lymphatic circulatory system of patients with several metastatic carcinomas is given in (Hong et al, 2016). They can range in size from 20 to 130 μm and contain up to 100 cells, with the metastatic potential of up to 50% higher than that of single cells (Umer et al, 2018;Lisencu et al, 2021). Significant advances have been reported regarding the molecular analysis of tumor clusters, nevertheless, the limitation of state-ofthe-art research with regard to the cluster cells dynamics process lies in the scarce information regarding the assessment of cell cluster velocity in relation to various factors such as cluster size or events (i.e., cluster division or unions).…”

The Role of Circulating Tumor Cells in the Prognosis of Metastatic Triple-Negative Breast Cancers: A Systematic Review of the Literature

“…These cells hold the ability of selfrenewal and tumorigenesis [10]. A part of these cells undergo an epithelial-mesenchymal transition (EMT) and become circulating tumor cells (CTCs) [13][14][15][16]. During EMT, CSCs undergo changes that lead to a shift from a stationary state into a migratory one.…”