Organotypic Models of Lung Cancer

Pomerenke, Anna

doi:10.1007/82_2017_79

Cited by 5 publications

(5 citation statements)

References 112 publications

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“…In a similar fashion, Takahashi et al used their high-throughput assay to evaluate 86 anti-cancer agents (molecular targeted drugs, immune checkpoint inhibitors and cytotoxic chemotherapies) in PDOs developed from lung tumors with squamous and adenosquamous histology [17]. In all these studies, the pharmacogenomic profiles of PDOs were highly comparable to that of tumor tissue indicating that organoid models can better predict individual therapeutic responses on a larger scale to inform therapeutic strategies over a reasonable time frame [55][56][57].…”

Section: Organoid Technology For High-throughput Drug Screeningmentioning

confidence: 99%

<em>Ex Vivo</em> Drug Testing of Patient-Derived Lung Organoids to Predict Treatment Responses for Personalized Medicine

Hung¹,

Williams²,

Williams³

et al. 2023

Preprint

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Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or biobanked sections/biopsy of lung tumors, PDXs, and pleural affusion. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and immune therapy agents. PDOs mainly recapitulated the genomic alterations, transcriptomic landscape and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remained, PDOs showed promise to screen novel therapy drugs. With the technical advance of high throughput, tumor-on-chip, combined microenvironment, and air-liquid interface (ALI), the drug screening using PDOs would serve better for precision care of lung cancer patients.

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Section: Organoid Technology For High-throughput Drug Screeningmentioning

confidence: 99%

<em>Ex Vivo</em> Drug Testing of Patient-Derived Lung Organoids to Predict Treatment Responses for Personalized Medicine

Hung¹,

Williams²,

Williams³

et al. 2023

Preprint

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“…Organ-like models of the respiratory tract have been established in recent years to mimic the 3D-formation and/or self-assembly of epithelial cells when cultured under certain conditions. The development of functional lung organoids is being discussed in order to better predict lung responses in vivo against toxins as well as in cancer studies [128,129]. These organoids have been used for cigarette smoke toxicity assessment [130].…”

Section: D In Vitro Modelsmentioning

confidence: 99%

In Vitro Systems for Toxicity Evaluation of Microbial Volatile Organic Compounds on Humans: Current Status and Trends

Cerimi

Jäckel

Meyer

et al. 2022

JoF

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Microbial volatile organic compounds (mVOC) are metabolic products and by-products of bacteria and fungi. They play an important role in the biosphere: They are responsible for inter- and intra-species communication and can positively or negatively affect growth in plants. But they can also cause discomfort and disease symptoms in humans. Although a link between mVOCs and respiratory health symptoms in humans has been demonstrated by numerous studies, standardized test systems for evaluating the toxicity of mVOCs are currently not available. Also, mVOCs are not considered systematically at regulatory level. We therefore performed a literature survey of existing in vitro exposure systems and lung models in order to summarize the state-of-the-art and discuss their suitability for understanding the potential toxic effects of mVOCs on human health. We present a review of submerged cultivation, air-liquid-interface (ALI), spheroids and organoids as well as multi-organ approaches and compare their advantages and disadvantages. Furthermore, we discuss the limitations of mVOC fingerprinting. However, given the most recent developments in the field, we expect that there will soon be adequate models of the human respiratory tract and its response to mVOCs.

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“…Peritoneal tissue models typically contain fibroblasts embedded in collagen I, as ovarian cancer cells have the highest level of adhesion and invasion in the presence of this ECM component [7]; such fibroblasts are topped with a monolayer of mesothelial cells. Tri-dimensional organotypic models of disease have shown, in many cancers, to provide different results than 2D assays in terms of cellular behavior or in drug responses [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

The metastatic capacity of high-grade serous ovarian cancer cells changes along disease progression: inhibition by mifepristone

et al. 2022

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Background Simplistic two-dimensional (2D) in vitro assays have long been the standard for studying the metastatic abilities of cancer cells. However, tri-dimensional (3D) organotypic models provide a more complex environment, closer to that seen in patients, and thereby provide a more accurate representation of their true capabilities. Our laboratory has previously shown that the antiprogestin and antiglucocorticoid mifepristone can reduce the growth, adhesion, migration, and invasion of various aggressive cancer cells assessed using 2D assays. In this study, we characterize the metastatic capabilities of high-grade serous ovarian cancer cells generated along disease progression, in both 2D and 3D assays, and the ability of cytostatic doses of mifepristone to inhibit them. Methods High-grade serous ovarian cancer cells collected from two separate patients at different stages of their disease were used throughout the study. The 2D wound healing and Boyden chamber assays were used to study migration, while a layer of extracellular matrix was added to the Boyden chamber to study invasion. A 3D organotypic model, composed of fibroblasts embedded in collagen I and topped with a monolayer of mesothelial cells was used to further study cancer cell adhesion and mesothelial displacement. All assays were studied in cells, which were originally harvested from two patients at different stages of disease progression, in the absence or presence of cytostatic doses of mifepristone. Results 2D in vitro assays demonstrated that the migration and invasive rates of the cells isolated from both patients decreased along disease progression. Conversely, in both patients, cells representing late-stage disease demonstrated a higher adhesion capacity to the 3D organotypic model than those representing an early-stage disease. This adhesive behavior is associated with the in vivo tumor capacity of the cells. Regardless of these differences in adhesive, migratory, and invasive behavior among the experimental protocols used, cytostatic doses of mifepristone were able to inhibit the adhesion, migration, and invasion rates of all cells studied, regardless of their basal capabilities over simplistic or organotypic metastatic in vitro model systems. Finally, we demonstrate that when cells acquire the capacity to grow spontaneously as spheroids, they do attach to a 3D organotypic model system when pre-incubated with conditioned media. Of relevance, mifepristone was able to cause dissociation of these multicellular structures. Conclusion Differences in cellular behaviours were observed between 2 and 3D assays when studying the metastatic capabilities of high-grade serous ovarian cancer cells representing disease progression. Mifepristone inhibited these metastatic capabilities in all assays studied.

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Organotypic Models of Lung Cancer

Cited by 5 publications

References 112 publications

<em>Ex Vivo</em> Drug Testing of Patient-Derived Lung Organoids to Predict Treatment Responses for Personalized Medicine

<em>Ex Vivo</em> Drug Testing of Patient-Derived Lung Organoids to Predict Treatment Responses for Personalized Medicine

In Vitro Systems for Toxicity Evaluation of Microbial Volatile Organic Compounds on Humans: Current Status and Trends

The metastatic capacity of high-grade serous ovarian cancer cells changes along disease progression: inhibition by mifepristone

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