Human gastric cancer modelling using organoids

Seidlitz, Therese; Merker, Sebastian R.; Rothe, Alexander; Zakrzewski, Falk; Neubeck, Cläre von; Grützmann, Konrad; Sommer, Ulrich; Schweitzer, Christine; Schölch, Sebastian; Uhlemann, Heike; Gaebler, Anne-Marlene; Werner, Kristin; Krause, Mechthild; Baretton, Gustavo; Welsch, Thilo; Koo, Bon–Kyoung; Aust, Daniela E.; Klink, Barbara; Weitz, Jürgen; Stange, Daniel E.

doi:10.1136/gutjnl-2017-314549

Cited by 219 publications

(207 citation statements)

References 42 publications

(37 reference statements)

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“…The in vitro and in vivo cancer models using organoids can bridge the traditional preclinical models and clinical trials with the advantages of being less time-consuming, more economic, and more effective [110]. Seidlitz et al [111] generated human and mouse GC organoids which modeled typical characteristics and altered pathways of human GC. These models revealed valuable information on the native tumor which can be used for drug screening and biomarker identification, thereby enabling precision medicines.…”

Section: Future Perspectivementioning

confidence: 99%

Emerging Role of Circulating Tumor Cells in Gastric Cancer

Huong

Gurshaney

Bình

et al. 2020

Cancers

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With over 1 million incidence cases and more than 780,000 deaths in 2018, gastric cancer (GC) was ranked as the 5th most common cancer and the 3rd leading cause of cancer deaths worldwide. Though several biomarkers, including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4), have been identified, their diagnostic accuracies were modest. Circulating tumor cells (CTCs), cells derived from tumors and present in body fluids, have recently emerged as promising biomarkers, diagnostically and prognostically, of cancers, including GC. In this review, we present the landscape of CTCs from migration, to the presence in circulation, biologic properties, and morphologic heterogeneities. We evaluated clinical implications of CTCs in GC patients, including diagnosis, prognosis, and therapeutic management, as well as their application in immunotherapy. On the one hand, major challenges in using CTCs in GC were analyzed, from the differences of cut-off values of CTC positivity, to techniques used for sampling, storage conditions, and CTC molecular markers, as well as the unavailability of relevant enrichment and detection techniques. On the other hand, we discussed future perspectives of using CTCs in GC management and research, including the use of circulating tumor microembolies; of CTC checkpoint blockade in immunotherapy; and of organoid models. Despite the fact that there are remaining challenges in techniques, CTCs have potential as novel biomarkers and/or a non-invasive method for diagnostics, prognostics, and treatment monitoring of GC, particularly in the era of precision medicine.

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Section: Future Perspectivementioning

confidence: 99%

Emerging Role of Circulating Tumor Cells in Gastric Cancer

Huong

Gurshaney

Bình

et al. 2020

Cancers

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“…In the PDO of gastric cancer, the patterns of resistance were documented [44]. In this study, PDOs were exposed to 5-FU, irinotecan, oxaliplatin, docetaxel, and epirubicin, and for each drug, various responses were documented.…”

Section: Patient-derived Organoid Analysis Of Drug Resistance In Precmentioning

confidence: 99%

Patient-derived organoid analysis of drug resistance in precision medicine: is there a value?

Abugomaa

Elbadawy

2020

Expert Review of Precision Medicine and Drug Development

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“…[ [153][154][155][156][157][158][159][160][161][162][163][164][165][166][167] Autism spectrum disorder (ASD) iPSCs derived from idiopathic ASD families [192] RETINA Leber congenital amaurosis Patient-derived iPSCs [193] STOMACH Gastric cancer Patients tumor biopsies [194][195][196][197] Gastric diseases due to Helicobacter pylori infection Gastric/esophageal tumor biopsies or commercial PSCs…”

Section: Bladdermentioning

confidence: 99%

Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

Argentati

Tortorella

Bazzucchi

et al. 2020

JPM

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Ex vivo cell/tissue-based models are an essential step in the workflow of pathophysiology studies, assay development, disease modeling, drug discovery, and development of personalized therapeutic strategies. For these purposes, both scientific and pharmaceutical research have adopted ex vivo stem cell models because of their better predictive power. As matter of a fact, the advancing in isolation and in vitro expansion protocols for culturing autologous human stem cells, and the standardization of methods for generating patient-derived induced pluripotent stem cells has made feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Furthermore, the potential of stem cells on generating more complex systems, such as scaffold-cell models, organoids, or organ-on-a-chip, allowed to overcome the limitations of the two-dimensional culture systems as well as to better mimic tissues structures and functions. Finally, the advent of genome-editing/gene therapy technologies had a great impact on the generation of more proficient stem cell-disease models and on establishing an effective therapeutic treatment. In this review, we discuss important breakthroughs of stem cell-based models highlighting current directions, advantages, and limitations and point out the need to combine experimental biology with computational tools able to describe complex biological systems and deliver results or predictions in the context of personalized medicine.Since their establishment, cell cultures have been proven to be the first and most powerful tool for the in vitro investigation of cell biology, from basic research to more complex translational approaches [6]. Classical two-dimensional (2D)-cultures usually consist of a unique type of cells (primary or continuous cultures) that grow in tissue culture polystyrene as adherent monolayers or in floating suspension, both in culture media that provide essential nutrients and growth factors. 2D-strategies are widely used to obtain a large number of cells, thus allowing the in vitro study of molecular mechanisms and development of metabolic assays [7-9]. However, due to their inability to recreate the in vivo complexity of the biological environment, they are not suitable for accurate disease modeling. These limitations have been overcome by the development of three-dimensional (3D)-cell cultures systems [10]. The rationale design of 3D-cell cultures is to harvest cells in microstructures that resemble tissues or organs shape and organization, thus allowing better cell-to-cell/cell-environment contacts and signaling crosstalk [11][12][13][14][15], essential events for tissues correct development and functioning [14,15]. The 3D-cell culture strategy is articulated in many different methods and techniques that can be grouped in scaffold-based or non-scaffold based platforms, each with particular advantages and disadvantages that make them useful for different applications [10,[16][17][18][19]. 3D-cell culture strategies are supported by the in silico...

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Human gastric cancer modelling using organoids

Abstract: We generated human and mouse gastric cancer organoids modelling typical characteristics and altered pathways of human gastric cancer. Successful interference with activated pathways demonstrates their potential usefulness as living biomarkers for therapy response testing.

Cited by 219 publications

References 42 publications

Emerging Role of Circulating Tumor Cells in Gastric Cancer

Emerging Role of Circulating Tumor Cells in Gastric Cancer

Patient-derived organoid analysis of drug resistance in precision medicine: is there a value?

Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises

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