Applications and Advances in Organoids for Cancer Research

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (1 March 2022) | Viewed by 11169

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Guest Editor
Sinonasal and Skull Base Tumor Program, Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Interests: cancer biology; olfactory neuroblastoma; organoids; sinonasal malignancies
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Special Issue Information

Dear colleagues,

The modeling of cancer biology through the development of tumor organoid models has undergone significant advances. A variety of organoid and three-dimensional culture models have been described to study the dynamic tumor pathophysiology, tissue–tissue interactions, and even the immune microenvironment. Potential applications of organoids in tumor biology include drug screening, immunotherapy, and personalized medicine. In this Special Issue, we will discuss recent developments and advances in organoid technology and three-dimensional culture models. Furthermore, we will highlight the applications of organoid models in the study of cancer biology.

Dr. Nyall London
Guest Editor

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Keywords

  • cancer biology
  • microfluidics
  • organoid
  • organoid-chip models
  • patient-derived organoid
  • spheroid
  • tumor biology

Published Papers (3 papers)

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18 pages, 5357 KiB  
Article
Designing Organoid Models to Monitor Cancer Progression, Plasticity and Resistance: The Right Set Up for the Right Question
by Flora Doffe, Fabien Bonini, Emile Lakis, Stéphane Terry, Salem Chouaib and Pierre Savagner
Cancers 2022, 14(15), 3559; https://doi.org/10.3390/cancers14153559 - 22 Jul 2022
Cited by 2 | Viewed by 2575
Abstract
The recent trend in 3D cell modeling has fostered the emergence of a wide range of models, addressing very distinct goals ranging from the fundamental exploration of cell–cell interactions to preclinical assays for personalized medicine. It is clear that no single model will [...] Read more.
The recent trend in 3D cell modeling has fostered the emergence of a wide range of models, addressing very distinct goals ranging from the fundamental exploration of cell–cell interactions to preclinical assays for personalized medicine. It is clear that no single model will recapitulate the complexity and dynamics of in vivo situations. The key is to define the critical points, achieve a specific goal and design a model where they can be validated. In this report, we focused on cancer progression. We describe our model which is designed to emulate breast carcinoma progression during the invasive phase. We chose to provide topological clues to the target cells by growing them on microsupports, favoring a polarized epithelial organization before they are embedded in a 3D matrix. We then watched for cell organization and differentiation for these models, adding stroma cells then immune cells to follow and quantify cell responses to drug treatment, including quantifying cell death and viability, as well as morphogenic and invasive properties. We used model cell lines including Comma Dβ, MCF7 and MCF10A mammary epithelial cells as well as primary breast cancer cells from patient-derived xenografts (PDX). We found that fibroblasts impacted cell response to Docetaxel and Palbociclib. We also found that NK92 immune cells could target breast cancer cells within the 3D configuration, providing quantitative monitoring of cell cytotoxicity. We also tested several sources for the extracellular matrix and selected a hyaluronan-based matrix as a promising alternative to mouse tumor basement membrane extracts for primary human cancer cells. Overall, we validated a new 3D model designed for breast cancer for preclinical use in personalized medicine. Full article
(This article belongs to the Special Issue Applications and Advances in Organoids for Cancer Research)
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15 pages, 1370 KiB  
Article
Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures
by Sara da Mata, Teresa Franchi-Mendes, Sofia Abreu, Bruno Filipe, Sónia Morgado, Marta Mesquita, Cristina Albuquerque, Ricardo Fonseca, Vítor E. Santo, Erwin R. Boghaert, Isadora Rosa and Catarina Brito
Cancers 2021, 13(18), 4695; https://doi.org/10.3390/cancers13184695 - 19 Sep 2021
Cited by 8 | Viewed by 3482
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced [...] Read more.
Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success. To improve clinical outcomes, translational models predictive of drug response are needed. We describe a simple method for the fast establishment of CRC patient-derived explant (CRC-PDE) cultures from different carcinogenesis pathways, employing agitation-based platforms. A total of 26 CRC-PDE were established and a subset was evaluated for viability (n = 23), morphology and genetic key alterations (n = 21). CRC-PDE retained partial tumor glandular architecture and microenvironment features were partially lost over 4 weeks of culture. Key proteins (p53 and Mismatch repair) and oncogenic driver mutations of the original tumours were sustained throughout the culture. Drug challenge (n = 5) revealed differential drug response from distinct CRC-PDE cases. These findings suggest an adequate representation of the original tumour and highlight the importance of detailed model characterisation. The preservation of key aspects of the CRC microenvironment and genetics supports CRC-PDE potential applicability in pre- and co-clinical settings, as long as temporal dynamics are considered. Full article
(This article belongs to the Special Issue Applications and Advances in Organoids for Cancer Research)
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19 pages, 2086 KiB  
Systematic Review
Patient-Derived Bladder Cancer Organoid Models in Tumor Biology and Drug Testing: A Systematic Review
by Benjamin Medle, Gottfrid Sjödahl, Pontus Eriksson, Fredrik Liedberg, Mattias Höglund and Carina Bernardo
Cancers 2022, 14(9), 2062; https://doi.org/10.3390/cancers14092062 - 20 Apr 2022
Cited by 16 | Viewed by 4376
Abstract
Bladder cancer is a common and highly heterogeneous malignancy with a relatively poor outcome. Patient-derived tumor organoid cultures have emerged as a preclinical model with improved biomimicity. However, the impact of the different methods being used in the composition and dynamics of the [...] Read more.
Bladder cancer is a common and highly heterogeneous malignancy with a relatively poor outcome. Patient-derived tumor organoid cultures have emerged as a preclinical model with improved biomimicity. However, the impact of the different methods being used in the composition and dynamics of the models remains unknown. This study aims to systematically review the literature regarding patient-derived organoid models for normal and cancer tissue of the bladder, and their current and potential future applications for tumor biology studies and drug testing. A PRISMA-compliant systematic review of the PubMED, Embase, Web of Sciences, and Scopus databases was performed. The results were analyzed based on the methodologies, comparison with primary tumors, functional analysis, and chemotherapy and immunotherapy testing. The literature search identified 536 articles, 24 of which met the inclusion criteria. Bladder cancer organoid models have been increasingly used for tumor biology studies and drug screening. Despite the heterogeneity between methods, organoids and primary tissues showed high genetic and phenotypic concordance. Organoid sensitivity to chemotherapy matched the response in patient-derived xenograft (PDX) models and predicted response based on clinical and mutation data. Advances in bioengineering technology, such as microfluidic devices, bioprinters, and imaging, are likely to further standardize and expand the use of organoids. Full article
(This article belongs to the Special Issue Applications and Advances in Organoids for Cancer Research)
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