Recent Advances in Microfluidic Platforms Applied in Cancer Metastasis: Circulating Tumor Cells' (CTCs) Isolation and Tumor‐On‐A‐Chip

Abstract

Cancer remains the leading cause of death worldwide despite the enormous efforts that are made in the development of cancer biology and anticancer therapeutic treatment. Furthermore, recent studies in oncology have focused on the complex cancer metastatic process as metastatic disease contributes to more than 90% of tumor‐related death. In the metastatic process, isolation and analysis of circulating tumor cells (CTCs) play a vital role in diagnosis and prognosis of cancer patients at an early stage. To obtain relevant information on cancer metastasis and progression from CTCs, reliable approaches are required for CTC detection and isolation. Additionally, experimental platforms mimicking the tumor microenvironment in vitro give a better understanding of the metastatic microenvironment and antimetastatic drugs' screening. With the advancement of microfabrication and rapid prototyping, microfluidic techniques are now increasingly being exploited to study cancer metastasis as they allow precise control of fluids in small volume and rapid sample processing at relatively low cost and with high sensitivity. Recent advancements in microfluidic platforms utilized in various methods for CTCs' isolation and tumor models recapitulating the metastatic microenvironment (tumor‐on‐a‐chip) are comprehensively reviewed. Future perspectives on microfluidics for cancer metastasis are proposed.

EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis

“…The prominent place progressively taken by microfluidics in the CTC field within the last decade is worth highlighting [19][20][21][22][23]. Microfluidics has indeed emerged as an innovative approach to directly process whole blood, to use small amounts of reagents, and to reduce cost.…”

“…Conversely, negative selection approaches have also been developed. If many of these systems use immunomagnetic sorting, microfluidic-based enrichment technologies have also emerged, in which different supports coated with specific antibodies are precisely disposed in the flow so as to favor cell-antibody interactions [19][20][21][22][23][24][25][26][27][28][29][30]. Interestingly, aptamers are gaining major interest as an alternative to antibodies in positive selection-based CTC enrichment, and have for instance been exploited in magnetic bead separation assays or in microfluidic devices [31,32].…”

Detection of circulating tumor cells: Advances and critical concerns (Review)

“…This can result in the loss of CTCs (8). Unlike the simple Ficoll-Hypaque separation, OncoQuick ® (Greiner Bio-One) incorporates a porous barrier during the separation process to prevent separated cells from mixing (76). This approach also has disadvantages.…”

Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction

“…ATM is a master controller of signaling networks, including DNA damage response (DDR), chromatin remodeling, cell growth, oxidative stress and senescence [24][25][26][27][28]. In addition, ATM signaling is involved in cancer, particularly in resistance to radio-and chemo-therapeutic treatment [29][30][31][32]. CK2 is a multifunctional protein kinase associated with a wide repertoire of substrates [33,34], which operates as a cancer driver by creating the cellular environment favorable to neoplasia [35].…”