Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology

Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Research on pancreatic cancer has transformed with the advent of organoid technology, providing a better platform that closely mimics biology in vivo. This review highlights critical advancements facilitated by models understanding disease progression, evaluating therapeutic responses, and identifying biomarkers. These three-dimensional cultures enable proper recapitulation cellular architecture genetic makeup original tumors, insights into complex molecular dynamics at various stages ductal adenocarcinoma (PDAC). We explore applications organoids dissecting tumor microenvironment (TME); elucidating metastasis, drug resistance mechanisms; personalizing strategies. By overcoming limitations traditional 2D animal models, use significantly accelerated translational research, which is promising for improving diagnostic approaches clinical settings, ultimately aiming to improve outcomes patients cancer.

Language: Английский

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Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e010579 - e010579

Published: Jan. 1, 2025

Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC described as a "cold" type with poor infiltration by cells factors leading intratumoral suppression have thus received less attention. Here, we identify mechanism that contributes cell-resistant phenotype describes potential combinatorial therapy. We used an unbiased screening approach of resistant sensitive murine KPC (KrasLSL-G12D/+; Trp53fl/fl; Ptf1aCre/+ ) three-dimensional co-culture platform syngeneic antigen-educated drivers PDAC. Comparative transcriptomic analysis was performed reveal promising candidates mediate resistance cells. investigated their contribution shRNA-mediated knockdown pharmacological inhibition vitro vivo studies, well patient-derived organoids (PDOs). A combination analyses, cytometric immunohistochemistry techniques allowed us validate underlying response phenotypes The action TGM2 via interaction tubulin impact microtubule dynamics vesicle trafficking were evaluated protein analyses live-cell imaging. Correlation TCGA data complemented functional studies. identified transglutaminase 2 (TGM2) mediator report high levels expression patients' tumors correlate immunosuppressive signatures overall survival. found regulates modulating network density pancreatic cells, facilitating secretion cytokines, which impair effector functionality. In TGM2-expressing PDOs, or treatment nocodazole increased cell-mediated apoptosis. Also, pretreatment TGM2high PDOs sublethal doses spindle poisons paclitaxel vincristine CD8+T activation sensitized toward cytotoxicity. These findings indicate targeting microtubular function therapeutically may enhance antitumor responses impacting activity cytokines microenvironment.

Language: Английский

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Establishing Pancreatic Cancer Organoids from EUS-Guided Fine-Needle Biopsy Specimens

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 692 - 692

Published: Feb. 18, 2025

Pancreatic cancer is a highly malignant digestive system tumor characterized by covert onset and rapid progression, with 5-year survival rate of less than 10%. Most patients have already reached an advanced or metastatic stage at the time diagnosis. Therefore, it particularly important to study occurrence, development, drug resistance mechanisms pancreatic cancer. In recent years, development 3D cell culture technology has provided new avenues for research. Patient-derived organoids (PDOs) are micro-organ structures that obtained directly from patient's body rapidly expand in vitro. PDOs ability self-renew self-organize retain genetic heterogeneity molecular characteristics original tumor. However, use limited because most ductal adenocarcinoma (PDAC) inoperable. Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) method obtaining tissue samples non-surgical patients. This article reviews factors affect formation using EUS-FNA/FNB. High-quality samples, sterile operations, optimized media key successfully generating organoids. Additionally, individual patient differences disease stages can impact constructed EUS-FNA/FNB significant potential, suggesting approaches research treatment.

Language: Английский

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B-Cell Co-culture in the Tumor Microenvironment of Solid Tumors Using Pancreatic Cancer as a Tumor Model

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown, P. 225 - 244

Published: Jan. 1, 2025

Language: Английский

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The use of patient-derived xenografts and patient-derived organoids in the search for new therapeutic regimens for pancreatic carcinoma. A review

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 182, P. 117750 - 117750

Published: Dec. 16, 2024

Language: Английский

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