Replacement, Reduction, and Refinement of Animal Experiments in Anticancer Drug Development: The Contribution of 3D In Vitro Cancer Models in the Drug Efficacy Assessment

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1058 - 1058

Published: March 30, 2023

In the last decades three-dimensional (3D) in vitro cancer models have been proposed as a bridge between bidimensional (2D) cell cultures and vivo animal models, gold standards preclinical assessment of anticancer drug efficacy. 3D can be generated through multitude techniques, from both immortalized lines primary patient-derived tumor tissue. Among them, spheroids organoids represent most versatile promising they faithfully recapitulate complexity heterogeneity human cancers. Although their recent applications include screening programs personalized medicine, not yet established tools for studying efficacy supporting preclinical-to-clinical translation, which remains mainly based on experimentation. this review, we describe state-of-the-art evaluation agents, focusing potential contribution to replace, reduce refine experimentations, highlighting strength weakness, discussing possible perspectives overcome current challenges.

Language: Английский

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Pancreatic cancer environment: from patient-derived models to single-cell omics

Molecular Omics, Journal Year: 2024, Volume and Issue: 20(4), P. 220 - 233

Published: Jan. 1, 2024

This review initially presents relevant patient-derived models, including PDXs, PDOs, and PDEs. Subsequently, a comprehensive summary of single-cell analyses conducted on these models is provided.

Language: Английский

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Advancing Tissue Decellularized Hydrogels for Engineering Human Organoids

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(29)

Published: May 22, 2022

Abstract The extracellular matrix plays a critical role in bioinstructing cellular self‐assembly and spatial (re)configuration processes that culminate human organoids vitro generation maturation. Considering the importance of supporting matrix, herein is showcased most recent advances bioengineering decellularized tissue hydrogels for generating assembloids. Key design blueprints, characterization methodologies, processing toolboxes are comprehensively discussed light current advances. Such enabling approaches provide grounds engineering next‐generation tissue‐specific with close‐to‐native biomolecular signatures user‐tailored biophysical properties may potentiate physiomimetic potential. In forward looking perspective, combination increasingly complex multicellular assemblies bottom‐up cell technologies unravel unprecedented tissue‐like physiological responses further advance exploitation assembloids as disease surrogates or patient‐tailored living therapeutics.

Language: Английский

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Challenges and Prospects of Patient-Derived Xenografts for Cancer Research

Cancers, Journal Year: 2023, Volume and Issue: 15(17), P. 4352 - 4352

Published: Aug. 31, 2023

We discuss the importance of in vivo models elucidating cancer biology, focusing on patient-derived xenograft (PDX) models, which are classic and standard functional platforms for preclinical evaluation. provide an overview most representative including cell-derived xenografts (CDX), tumor metastatic xenografts, PDX utilizing humanized mice (HM). The orthotopic could reproduce environment its progression, similar to human tumors, particularly common. procedures rationales gastric adenocarcinoma (GAC) addressed. Despite significant advantages such as recapitulating key features tumors enabling drug testing context, some challenges must be acknowledged, loss heterogeneity, selection bias, clonal evolution, stroma replacement, micro-environment (TME) changes, host cell carryover contaminations, human-to-host oncogenic transformation, viral infections, well limitations immunologic research. To compensate these limitations, other mouse syngeneic currently utilized. Overall, represent a powerful tool research, providing critical insights into biology potential therapeutic targets, but their carefully considered effective use. Lastly, we present intronic quantitative PCR (qPCR) method authenticate, detect, quantify human/murine cells lines samples.

Language: Английский

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Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer

Bioactive Materials, Journal Year: 2023, Volume and Issue: 25, P. 360 - 373

Published: Feb. 15, 2023

The tumor microenvironment consists of diverse, complex etiological factors. matrix component pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could fully recapitulate the etiology mimic understand PDAC. Here, two major components matrices, hyaluronic acid- gelatin-based hydrogels, are engineered provide matrices for spheroids composed PDAC cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes a more compact formation. Higher expression levels markers associated with proliferation, epithelial mesenchymal transition, mechanotransduction, observed cancer-CAF cultured hyper matrix-mimicking while trend can be when those hydrogels presence transforming growth factor-β1 (TGF-β1). proposed multicellular model, combination proper mechanical TGF-β1 supplement, makes strides developing advanced resembling monitoring tumors, which potentially applicable realizing personalized medicine drug testing applications.

Language: Английский

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Boosting Energy Deprivation by Synchronous Interventions of Glycolysis and Oxidative Phosphorylation for Bioenergetic Therapy Synergetic with Chemodynamic/Photothermal Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: March 15, 2024

Abstract Bioenergetic therapy is emerging as a promising therapeutic approach. However, its effectiveness restricted by metabolic plasticity, tumor cells switch phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) to compensate for energy. Herein, Metformin (MET) BAY‐876 (BAY) co‐loaded CuFe 2 O 4 (CF) nanoplatform (CFMB) developed boost energy deprivation synchronous interventions of OXPHOS bioenergetic synergetic with chemodynamic/photothermal (CDT/PTT). The MET can simultaneously restrain inhibiting hexokinase (HK2) activity damaging mitochondrial function deprive energy, respectively. Besides, BAY blocks glucose uptake transporter 1 (GLUT1) expression, further potentiating the repression thus achieving much more depletion tumorigenic sources. Interestingly, upregulated antioxidant glutathione (GSH) in cancer triggers CFMB degradation release Cu + /Fe 2+ catalyzing tumor‐overexpressed H hydroxyl radical (∙OH), both impairing GSH‐depletion amplified CDT. Furthermore, upon near‐infrared (NIR) light irradiation, has photothermal conversion capacity kill PTT improve ∙OH production enhanced In vivo experiments have manifested that remarkably suppressed growth mice without systemic toxicity. This study provides new modality paradigm bioenergetic‐related therapies.

Language: Английский

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Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 62 - 62

Published: Jan. 8, 2025

Background: Tumors, as intricate ecosystems, comprise oncocytes and the highly dynamic tumor stroma. Tumor stroma, representing non-cancerous non-cellular composition of microenvironment (TME), plays a crucial role in oncogenesis progression, through its interactions with biological, chemical, mechanical signals. This review aims to analyze challenges stroma mimicry models, highlight advanced personalized co-culture approaches for recapitulating using patient-derived organoids (PDTOs). Methods: synthesizes findings from recent studies on composition, stromal remodeling, spatiotemporal heterogeneities TME. It explores popular stroma-related systems integrating PDTOs elements, techniques improve mimicry. Results: Stroma driven by cells, highlights dynamism heterogeneity PDTOs, derived tissues or cancer-specific stem accurately mimic tissue-specific genetic features primary tumors, making them valuable drug screening. Co-culture models combining elements effectively recreate TME, showing promise anti-cancer therapy. Advanced flexible combinations enhance precision tumor-stroma recapitulation. Conclusions: PDTO-based offer promising platform therapy development. underscores importance refining these advance medicine therapeutic outcomes.

Language: Английский

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3D-bioprinted cancer-on-a-chip: level-up organotypic in vitro models

Trends in biotechnology, Journal Year: 2021, Volume and Issue: 40(4), P. 432 - 447

Published: Sept. 20, 2021

Language: Английский

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Targeting Tumor-Stromal Interactions in Pancreatic Cancer: Impact of Collagens and Mechanical Traits

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Nov. 25, 2021

Pancreatic ductal adenocarcinoma (PDAC) has one of the worst outcomes among cancers with a 5-years survival rate below 10%. This is result late diagnosis and lack effective treatments. The tumor characterized by highly fibrotic stroma containing distinct cellular components, embedded within an extracellular matrix (ECM). ECM-abundant microenvironment (TME) in PDAC plays pivotal role progression resistance to treatment. Cancer-associated fibroblasts (CAFs), being dominant cell type stroma, are fact functionally heterogeneous populations cells TME. Certain subtypes CAFs main producer ECM components most abundant collagen family proteins. Collagens large macromolecules that upon deposition into form supramolecular fibrillar structures which provide mechanical framework They not only bring structure tissue structural proteins but also contain binding domains interact surface receptors on cancer cells. These interactions can induce various responses activate signaling pathways leading epithelial-to-mesenchymal transition (EMT) ultimately metastasis. In addition, collagens contributors building up forces tumor. influence involved motility affect microstructure stiffness exerting solid stress interstitial fluid pressure Taken together, TME subjected types progression, metastasis, drug response. this review article, we aim summarize contextualize recent knowledge especially different traits progression. We furthermore discuss experimental models available for studying tumor-stromal finally potential therapeutic targets stroma.

Language: Английский

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3D Tumor Spheroid and Organoid to Model Tumor Microenvironment for Cancer Immunotherapy

Organoids, Journal Year: 2022, Volume and Issue: 1(2), P. 149 - 167

Published: Dec. 5, 2022

The intricate microenvironment in which malignant cells reside is essential for the progression of tumor growth. Both physical and biochemical features (TME) play a critical role promoting differentiation, proliferation, invasion, metastasis cancer cells. It therefore to understand how interact communicate with an assortment supportive tumor-associated including macrophages, fibroblasts, endothelial cells, other immune To study complex mechanisms behind progression, 3D spheroid organoid models are widely favor because they replicate stromal environment multicellular structure present within vivo tumor. provides more precise data about cell–cell interactions, characteristics, drug discovery, metabolic profile compared oversimplified 2D systems unrepresentative animal models. This review description key elements as well early research using cell-line derived, that paved way adoption patient-derived In particular, provide method screening particular emphasis on influence TME immunotherapy.

Language: Английский

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