scholarly journals Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4192
Author(s):  
Santa Bērziņa ◽  
Alexandra Harrison ◽  
Valérie Taly ◽  
Wenjin Xiao
Keyword(s):  
Tumor Model ◽  
Cancer Therapies ◽  
Analysis Tools ◽  
Chip Technology ◽  
Technological Advances ◽  
Anti Cancer ◽  
On Chip ◽  
Chip Analysis

Tumor-on-chip technology has cemented its importance as an in vitro tumor model for cancer research. Its ability to recapitulate different elements of the in vivo tumor microenvironment makes it promising for translational medicine, with potential application in enabling personalized anti-cancer therapies. Here, we provide an overview of the current technological advances for tumor-on-chip generation. To further elevate the functionalities of the technology, these approaches need to be coupled with effective analysis tools. This aspect of tumor-on-chip technology is often neglected in the current literature. We address this shortcoming by reviewing state-of-the-art on-chip analysis tools for microfluidic tumor models. Lastly, we focus on the current progress in tumor-on-chip devices using patient-derived samples and evaluate their potential for clinical research and personalized medicine applications.

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

scholarly journals Importance of T, NK, CAR T and CAR NK Cell Metabolic Fitness for Effective Anti-Cancer Therapy: A Continuous Learning Process Allowing the Optimization of T, NK and CAR-Based Anti-Cancer Therapies

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 183
Author(s):  
Adrien Krug ◽  
Adriana Martinez-Turtos ◽  
Els Verhoeyen
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Building Blocks ◽  
Cancer Therapies ◽  
Cell Therapies ◽  
Anti Cancer ◽  
Car T ◽  
Metabolic Fitness

Chimeric antigen receptor (CAR) T and CAR NK cell therapies opened new avenues for cancer treatment. Although original successes of CAR T and CAR NK cells for the treatment of hematological malignancies were extraordinary, several obstacles have since been revealed, in particular their use for the treatment of solid cancers. The tumor microenvironment (TME) is competing for nutrients with T and NK cells and their CAR-expressing counterparts, paralyzing their metabolic effective and active states. Consequently, this can lead to alterations in their anti-tumoral capacity and persistence in vivo. High glucose uptake and the depletion of key amino acids by the TME can deprive T and NK cells of energy and building blocks, which turns them into a state of anergy, where they are unable to exert cytotoxic activity against cancer cells. This is especially true in the context of an immune-suppressive TME. In order to re-invigorate the T, NK, CAR T and CAR NK cell-mediated antitumor response, the field is now attempting to understand how metabolic pathways might change T and NK responses and functions, as well as those from their CAR-expressing partners. This revealed ways to metabolically rewire these cells by using metabolic enhancers or optimizing pre-infusion in vitro cultures of these cells. Importantly, next-generation CAR T and CAR NK products might include in the future the necessary metabolic requirements by improving their design, manufacturing process and other parameters. This will allow the overcoming of current limitations due to their interaction with the suppressive TME. In a clinical setting, this might improve their anti-cancer effector activity in synergy with immunotherapies. In this review, we discuss how the tumor cells and TME interfere with T and NK cell metabolic requirements. This may potentially lead to therapeutic approaches that enhance the metabolic fitness of CAR T and CAR NK cells, with the objective to improve their anti-cancer capacity.

scholarly journals Advanced Microengineered Lung Models for Translational Drug Discovery

2018 ◽  
Vol 23 (8) ◽  
pp. 777-789 ◽  
Author(s):  
Brian F. Niemeyer ◽  
Peng Zhao ◽  
Rubin M. Tuder ◽  
Kambez H. Benam
Keyword(s):  
Biomarker Discovery ◽  
Human Lung ◽  
In Vivo Models ◽  
Chip Technology ◽  
Preclinical Drug Development ◽  
Lung Alveolus ◽  
Organ Level ◽  
On Chip

Lung diseases impose a significant socioeconomic burden and are a leading cause of morbidity and mortality worldwide. Moreover, respiratory medicine, unlike several other therapeutic areas, faces a disappointingly low number of new approved therapies. This is partly due to lack of reliable in vitro or in vivo models that can reproduce organ-level complexity and pathophysiological responses of human lung. Here, we examine new opportunities in application of recently emerged organ-on-chip technology to model human lung alveolus and small airway in preclinical drug development and biomarker discovery. We also discuss challenges that need to be addressed in coming years to further enhance the physiological and clinical relevance of these microsystems, enable their increased accessibility, and support their leap into personalized medicine.

scholarly journals Immunotherapy-on-chip Against an Experimental Sepsis Model

2021 ◽  
Author(s):  
Ioanna Zerva ◽  
Katerina Bakela ◽  
Irene Athanassakis
Keyword(s):  
Micrococcus Luteus ◽  
Experimental Sepsis ◽  
Immunostimulatory Activity ◽  
Cd8 Cells ◽  
Arginase 1 ◽  
Chip Technology ◽  
On Chip ◽  
Lps Treatment

Abstract Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip technology in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS, allowing longer survival, necessary for a therapeutic treatment application. A novel immunotherapy technology, the so-called vaccine-on-chip consists of a 3-dimentional laser micro-textured silicon (Si)-scaffold loaded with macrophages and activated in vitro with 1μg/ml PG, which has been previously shown to exert a mild immunostimulatory activity upon subcutaneous implantation. The LPS treatment significantly decreased CD4+ and CD8+ cells, while increasing CD11b+, Gr1+, CD25+, Foxp3+ and class II+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and C-reactive protein (CRP), procalcitonin (PCT), IL-6, TNF-a, IL-10 and IL-18 in the serum, while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated implant significantly increased the percentage of CD4+ and CD8+ cells, while decreasing the percentage of Gr1+, CD25+, CD11b+, Foxp3+ cells and arginase-1 activity in the spleen of LPS-treated animals, as well as all serum markers tested, allowing survival and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a novel immunotherapy technology based on PG pre-activated micro-texture Si-scaffolds in LPS endotoxemia, supporting thus its potential use in the treatment of septic patients.

scholarly journals Recapitulating the Vasculature Using Organ-On-Chip Technology

2020 ◽  
Vol 7 (1) ◽  
pp. 17 ◽  
Author(s):  
Andreas M.A.O. Pollet ◽  
Jaap M.J. den Toonder
Keyword(s):  
Advantages And Disadvantages ◽  
Biological Relevance ◽  
Chip Technology ◽  
Intrinsic Complexity ◽  
On Chip

The development of Vasculature-on-Chip has progressed rapidly over the last decade and recently, a wealth of fabrication possibilities has emerged that can be used for engineering vessels on a chip. All these fabrication methods have their own advantages and disadvantages but, more importantly, the capability of recapitulating the in vivo vasculature differs greatly between them. The first part of this review discusses the biological background of the in vivo vasculature and all the associated processes. We then evaluate the biological relevance of different fabrication methods proposed for Vasculature-on-Chip, we indicate their possibilities and limitations, and we assess which fabrication methods are capable of recapitulating the intrinsic complexity of the vasculature. This review illustrates the complexity involved in developing in vitro vasculature and provides an overview of fabrication methods for Vasculature-on-Chip in relation to the biological relevance of such methods.

scholarly journals LDHA Suppression Altering Metabolism Inhibits Tumor Progress by an Organic Arsenical

2019 ◽  
Vol 20 (24) ◽  
pp. 6239
Author(s):  
Yu-Jiao Liu ◽  
Xiao-Yang Fan ◽  
An-Dong Wang ◽  
Yin-Zheng Xia ◽  
Wen-Rong Fu ◽  
...  
Keyword(s):  
Cancer Therapies ◽  
Therapeutic Value ◽  
Metabolic Remodeling ◽  
Anti Cancer ◽  
Tumor Progress ◽  
Caspase Family ◽  
Dependent Cell ◽  
Ros Burst

Based on the potential therapeutic value in targeting metabolism for the treatment of cancer, an organic arsenical PDT-BIPA was fabricated, which exerted selective anti-cancer activity in vitro and in vivo via targeting lactate dehydrogenase A (LDHA) to remodel the metabolic pathway. In details, the precursor PDT-BIPA directly inhibited the function of LDHA and converted the glycolysis to oxidative phosphorylation causing ROS burst and mitochondrial dysfunction. PDT-BIPA also altered several gene expression, such as HIF-1α and C-myc, to support the metabolic remodeling. All these changes lead to caspase family-dependent cell apoptosis in vivo and in vitro without obvious side effect. Our results provided this organic arsenical precursor as a promising anticancer candidate and suggested metabolism as a target for cancer therapies.

scholarly journals Phycocyanin from Arthrospira platensis as Potential Anti-Cancer Drug: Review of In Vitro and In Vivo Studies

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 91
Author(s):  
Steffen Braune ◽  
Anne Krüger-Genge ◽  
Sarah Kammerer ◽  
Friedrich Jung ◽  
Jan-Heiner Küpper
Keyword(s):  
Molecular Mechanisms ◽  
Arthrospira Platensis ◽  
Water Soluble ◽  
In Vivo Studies ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Natural Substances ◽  
Anti Cancer

The application of cytostatic drugs or natural substances to inhibit cancer growth and progression is an important and evolving subject of cancer research. There has been a surge of interest in marine bioresources, particularly algae, as well as cyanobacteria and their bioactive ingredients. Dried biomass products of Arthrospira and Chlorella have been categorized as “generally recognized as safe” (GRAS) by the US Food and Drug Administration (FDA). Of particular importance is an ingredient of Arthrospira: phycocyanin, a blue-red fluorescent, water-soluble and non-toxic biliprotein pigment. It is reported to be the main active ingredient of Arthrospira and was shown to have therapeutic properties, including anti-oxidant, anti-inflammatory, immune-modulatory and anti-cancer activities. In the present review, in vitro and in vivo data on the effects of phycocyanin on various tumor cells and on cells from healthy tissues are summarized. The existing knowledge of underlying molecular mechanisms, and strategies to improve the efficiency of potential phycocyanin-based anti-cancer therapies are discussed.

scholarly journals Functional properties of ion channels and transporters in tumour vascularization

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130103 ◽  
Author(s):  
Alessandra Fiorio Pla ◽  
Luca Munaron
Keyword(s):  
Ion Channels ◽  
Endothelial Cell Proliferation ◽  
Cancer Therapies ◽  
Tumour Angiogenesis ◽  
Anti Cancer ◽  
Solid Tumour Growth ◽  
Tumour Vascularization

Vascularization is crucial for solid tumour growth and invasion, providing metabolic support and sustaining metastatic dissemination. It is now accepted that ion channels and transporters play a significant role in driving the cancer growth at all stages. They may represent novel therapeutic, diagnostic and prognostic targets for anti-cancer therapies. On the other hand, although the expression and role of ion channels and transporters in the vascular endothelium is well recognized and subject of recent reviews, only recently has their involvement in tumour vascularization been recognized. Here, we review the current literature on ion channels and transporters directly involved in the angiogenic process. Particular interest will be focused on tumour angiogenesis in vivo as well as in the different steps that drive this process in vitro , such as endothelial cell proliferation, migration, adhesion and tubulogenesis. Moreover, we compare the ‘transportome’ system of tumour vascular network with the physiological one.

scholarly journals Emerging Neuroblastoma 3D In Vitro Models for Pre-Clinical Assessments

2020 ◽  
Vol 11 ◽  
Author(s):  
Diana Corallo ◽  
Stella Frabetti ◽  
Olivia Candini ◽  
Elisa Gregianin ◽  
Massimo Dominici ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Structural Complexity ◽  
3D Cell Culture ◽  
Cell Types ◽  
In Vitro Models ◽  
Cancer Therapies ◽  
Extracellular Matrix Components ◽  
Anti Cancer

The potential of tumor three-dimensional (3D) in vitro models for the validation of existing or novel anti-cancer therapies has been largely recognized. During the last decade, diverse in vitro 3D cell systems have been proposed as a bridging link between two-dimensional (2D) cell cultures and in vivo animal models, both considered gold standards in pre-clinical settings. The latest awareness about the power of tailored therapies and cell-based therapies in eradicating tumor cells raises the need for versatile 3D cell culture systems through which we might rapidly understand the specificity of promising anti-cancer approaches. Yet, a faithful reproduction of the complex tumor microenvironment is demanding as it implies a suitable organization of several cell types and extracellular matrix components. The proposed 3D tumor models discussed here are expected to offer the required structural complexity while also assuring cost-effectiveness during pre-selection of the most promising therapies. As neuroblastoma is an extremely heterogenous extracranial solid tumor, translation from 2D cultures into innovative 3D in vitro systems is particularly challenging. In recent years, the number of 3D in vitro models mimicking native neuroblastoma tumors has been rapidly increasing. However, in vitro platforms that efficiently sustain patient-derived tumor cell growth, thus allowing comprehensive drug discovery studies on tailored therapies, are still lacking. In this review, the latest neuroblastoma 3D in vitro models are presented and their applicability for a more accurate prediction of therapy outcomes is discussed.

scholarly journals Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies

2021 ◽  
Vol 11 ◽  
Author(s):  
Andrew M. K. Law ◽  
Laura Rodriguez de la Fuente ◽  
Thomas J. Grundy ◽  
Guocheng Fang ◽  
Fatima Valdes-Mora ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
3D Culture ◽  
3D Cell Culture ◽  
Cancer Therapeutics ◽  
Drug Efficacy ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

Over 90% of potential anti-cancer drug candidates results in translational failures in clinical trials. The main reason for this failure can be attributed to the non-accurate pre-clinical models that are being currently used for drug development and in personalised therapies. To ensure that the assessment of drug efficacy and their mechanism of action have clinical translatability, the complexity of the tumor microenvironment needs to be properly modelled. 3D culture models are emerging as a powerful research tool that recapitulates in vivo characteristics. Technological advancements in this field show promising application in improving drug discovery, pre-clinical validation, and precision medicine. In this review, we discuss the significance of the tumor microenvironment and its impact on therapy success, the current developments of 3D culture, and the opportunities that advancements that in vitro technologies can provide to improve cancer therapeutics.

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