Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 3, 2025

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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Experimental Murine Models for Colorectal Cancer Research

Cancers, Journal Year: 2023, Volume and Issue: 15(9), P. 2570 - 2570

Published: April 30, 2023

Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and in both sexes. Numerous animal models for CRC have been established to study its biology, namely carcinogen-induced (CIMs) genetically engineered mouse (GEMMs). CIMs are valuable assessing colitis-related carcinogenesis studying chemoprevention. On other hand, GEMMs proven be useful evaluating tumor microenvironment systemic immune responses, which contributed discovery of novel therapeutic approaches. Although metastatic disease can induced by orthotopic injection cell lines, resulting not representative full genetic diversity due limited number lines suitable this purpose. patient-derived xenografts (PDX) reliable preclinical drug development their ability retain pathological molecular characteristics. In review, authors discuss various murine with a focus on clinical relevance, benefits, drawbacks. From all discussed, will continue an important tool advancing our understanding treatment disease, but additional research required find model that correctly reflect pathophysiology CRC.

Language: Английский

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Large inherent variability in data derived from highly standardised cell culture experiments

Pharmacological Research, Journal Year: 2023, Volume and Issue: 188, P. 106671 - 106671

Published: Jan. 18, 2023

Cancer drug development is hindered by high clinical attrition rates, which are blamed on weak predictive power preclinical models and limited replicability of findings. However, the technically feasible level remains unknown. To fill this gap, we conducted an analysis data from NCI60 cancer cell line screen (2.8 million compound/cell experiments), to our knowledge largest depository experiments that have been repeatedly performed over decades. The findings revealed profound intra-laboratory variability, although all were executed following highly standardised protocols avoid known confounders quality. All compound/ combinations with > 100 independent biological replicates displayed maximum GI50 (50% growth inhibition) fold changes (highest/ lowest GI50) 5% 70.5% 1000. highest change was 3.16 × 1010 (lowest GI50: 7.93 ×10-10 µM, 25.0 µM). FDA-approved drugs experimental agents similar variation. Variability remained after outlier removal, when only considering tested at same concentration range, NCI60-provided quality-controlled data. In conclusion, variability intrinsic feature anti-cancer testing, even among in a world-leading research environment. Awareness inherent will support realistic interpretation inspire improve robustness. Further show whether inclusion wider variety model systems, such as animal and/ or patient-derived models, may

Language: Английский

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A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine

Cellular Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: May 28, 2024

Cancer is a highly heterogeneous disease, and thus treatment responses vary greatly between patients. To improve therapy efficacy outcome for cancer patients, more representative patient-specific preclinical models are needed. Organoids tumoroids 3D cell culture that typically retain the genetic epigenetic characteristics, as well morphology, of their tissue origin. Thus, they can be used to understand underlying mechanisms initiation, progression, metastasis in physiological setting. Additionally, co-culture methods cancer-associated cells help interplay tumor its microenvironment. In recent years, have already helped refine treatments identify new targets therapy. Advanced culturing systems such chip-based fluidic devices bioprinting combination with been high-throughput applications personalized medicine. Even though organoid tumoroid complex vitro systems, validation results vivo still common practice. Here, we describe how both animal- human-derived novel vulnerabilities currently precision

Language: Английский

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Visualization of Vascular Perfusion of Human Pancreatic Cancer Tissue in the CAM Model and Its Impact on Future Personalized Drug Testing

Organoids, Journal Year: 2024, Volume and Issue: 3(1), P. 1 - 17

Published: Jan. 8, 2024

Although significant improvements have been made in the treatment of pancreatic cancer, its prognosis remains poor with an overall 5-year survival rate less than 10%. New experimental approaches are necessary to develop novel therapeutics. In this study, investigation cancer tissue growth chorioallantoic membrane (CAM) model and subsequent use indocyanine green (ICG) injections for verification intratumoral perfusion was conducted. ICG injected into CAM vasculature visualize tumor tissue. The presence metastasis investigated through PCR human-specific ALU element liver chicken embryo. Additionally, usage cryopreserved tumors established. Intratumoral on observed recently obtained tumors. ALU-PCR detected chick embryos’ livers. After cryopreservation, still vital, xenografts generated from these resembled histological features primary tumor. This methodology represents proof principle intravenous drug testing model. can be used therapeutics integrated molecular board, facilitating personalized treatment.

Language: Английский

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Recent applications of three-dimensional bioprinting in drug discovery and development

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 115456 - 115456

Published: Sept. 1, 2024

Language: Английский

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Patient-derived xenograft models: Current status, challenges, and innovations in cancer research

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101520 - 101520

Published: Jan. 1, 2025

Language: Английский

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Antitumor activity of gilteritinib, an inhibitor of AXL, in human solid tumors

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 29, 2025

AXL, a receptor tyrosine kinase, has recently emerged as potential therapeutic target against various types of cancer. Gilteritinib, FDA-approved small-molecule inhibitor, is used for the treatment patients with FLT3-mutated acute myeloid leukemia. However, antitumor activity gilteritinib in solid tumors remains poorly elucidated. In this study, we explored AXL-expressing esophageal cancer (EC), ovarian (OC), and gastric (GC), along underlying molecular mechanisms. Our data demonstrated that significantly inhibited cell proliferation spheroid formation by triggering apoptosis cycle arrest AXL-positive EC, OC, GC cells. Moreover, found repressed migration invasion. Mechanistically, RNA-seq analysis revealed downregulated multiple cancer-related pathways, including those related to apoptosis, cycle, mTOR pathway, AMPK p53 FOXO Hippo Wnt pathway. Gilteritinib unique set E2F- MYC target-associated genes Intriguingly, interrogation cohort these were overexpressed associated poor prognosis. also displayed strong effects on PDX-derived explants (PDXEs) organoids (PDXOs) ex vivo PDXs vivo. Collectively, findings reveal represents potent agent tumors. Zhang et al. demonstrate superior efficacy cancer, lines, PDXOs models. This work highlights novel approach

Language: Английский

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HDACIs and TKIs combinations and their liposomal delivery for cancer treatment

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 358, P. 59 - 77

Published: April 28, 2023

Fixed-drug combinations have been used for the treatment of cancer. Current anticancer therapies, however, tend to induce resistance and provoke important toxicity. Therefore, there is still a need further optimized treatments that would also take into account drug-drug interactions. Tyrosine kinase inhibitors (TKIs) Histone deacetylase (HDACIs) are two drug classes currently separately in clinical practice. Those being investigated trials. Several findings confirm safety tolerability these accompanied by improvement. The activity specificity can be improved employing appropriate delivery systems, such as nanocarrier systems. different pharmacokinetic profiles each may lead loss synergistic effects, affecting efficiency. either TKI or HDACI with an another class co-loaded inside liposomal carriers vivo show promising results terms efficacy safety. In this review we discuss strategies cancer treatment.

Language: Английский

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