Tumor Models and Drug Targeting In Vitro—Where Are We Today? Where Do We Go from Here?

Krüger, Marcus; Kopp, Sascha

doi:10.3390/cancers15061768

Cited by 4 publications

(6 citation statements)

References 30 publications

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“…While a decent cluster of in vitro microtumor models has been reported, most of these models were developed based on closed-system microfluidics. [43] The closed-system configuration is not well aligned with the open system standard in biology and biomedicine, adding adoption and implementation barriers to the end users (e.g., biologists, oncologists) where the most impact is expected to see from using these models.…”

Section: Discussionmentioning

confidence: 99%

Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis

Li,

Argall-Knapp

et al. 2024

Preprint

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Using a combined top-down (i.e., operator-directed) and bottom-up (i.e., cell-directed) strategy, we present an Under-oil Open Microfluidic System (UOMS)-based microtumor model for investigating tumor cell migration and anti-metastasis drug test. Compared to the mainstream closed microfluidics-based microtumor models, the UOMS microtumor model features: i) micrometer-scale lateral resolution of surface patterning with open microfluidic design for flexible spatiotemporal sample manipulation (i.e., top-down); ii) self-organized extracellular matrix (ECM) structures and tumor cell-ECM spontaneous remodeling (i.e., bottom-up); and iii) free physical access to the samples on a device with minimized system disturbance. The UOMS microtumor model is used to test an anti-metastasis drug (incyclinide, aka CMT-3) with a triple negative breast cancer cell line (MDA-MB-231). Thein vitroresults show a suppression of tumor cell migration and ECM remodeling echoing with thein vivomice metastasis results.

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Section: Discussionmentioning

confidence: 99%

Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis

Li,

Argall-Knapp

et al. 2024

Preprint

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“…The results of preclinical studies quite often do not predict the outcome in cancer patients; thus, the research on potential chemical agents does not proceed to clinical development. The gap between 2D cell cultures and animal models can be bridged by complex three-dimensional systems that closely recapitulate the course of human cancer [ 2 , 116 , 144 , 156 , 171 ]. Recent developments in three-dimensional, microfluidic, and multicellular systems used for neuroblastoma research [ 150 ] are promising, especially for testing new therapeutic approaches [ 118 , 160 , 253 , 254 ], including natural product research [ 177 ], immunotherapy [ 172 , 255 , 256 ], and new multimodal strategies for high-risk neuroblastoma [ 149 ].…”

Section: Discussionmentioning

confidence: 99%

“…The heterogeneity of the tumor is currently described not only as a difference between the cancer cells in morphology, transcriptional profiles, and metabolism, but also includes the differences between the tumor microenvironment, which plays an important role in tumor resistance to therapy, the higher level of metastasis, and aggressiveness [ 113 , 114 , 115 ]. With two-dimensional cell lines, we are not able to properly reproduce these conditions in vitro [ 2 , 5 , 11 , 26 , 116 ].…”

Section: In Vitro Models Of Neuroblastomamentioning

confidence: 99%

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Preclinical Models of Neuroblastoma—Current Status and Perspectives

Krawczyk

Kitlińska

2023

Cancers

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Preclinical in vitro and in vivo models remain indispensable tools in cancer research. These classic models, including two- and three-dimensional cell culture techniques and animal models, are crucial for basic and translational studies. However, each model has its own limitations and typically does not fully recapitulate the course of the human disease. Therefore, there is an urgent need for the development of novel, advanced systems that can allow for efficient evaluation of the mechanisms underlying cancer development and progression, more accurately reflect the disease pathophysiology and complexity, and effectively inform therapeutic decisions for patients. Preclinical models are especially important for rare cancers, such as neuroblastoma, where the availability of patient-derived specimens that could be used for potential therapy evaluation and screening is limited. Neuroblastoma modeling is further complicated by the disease heterogeneity. In this review, we present the current status of preclinical models for neuroblastoma research, discuss their development and characteristics emphasizing strengths and limitations, and describe the necessity of the development of novel, more advanced and clinically relevant approaches.

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“…These models have the common goal of investigating the response of a cancer to a (combination of) treatment(s). When selecting a preclinical model, several parameters are to be considered, such as experimental duration, long-term effects, the intricacies of the tumor, and the inclusion of Tumor Micro-Environment (TME), something that is difficult to recapitulate in most in vitro models [7,8].…”

Section: Introductionmentioning

confidence: 99%

Zebrafish avatars: towards functional precision medicine in low-grade serous ovarian cancer

Fieuws,

Bek,

Parton

et al. 2024

Preprint

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Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines, and 3D tumor models. To address this goal, a well characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G > T (p.(Gly12Val)) was used. Fluorescently labelled tumor cells were injected into the perivitelline space of 2 days post fertilization zebrafish embryos. At 1 day post-injection xenografts were as-sessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib, and trametinib + luminespib. Subsequently xenografts were euthanized and analysed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n=84) in vivo and with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC.

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Tumor Models and Drug Targeting In Vitro—Where Are We Today? Where Do We Go from Here?

Abstract: Cancer is one of the leading causes of death worldwide [...]

Cited by 4 publications

References 30 publications

Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis

Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis

Preclinical Models of Neuroblastoma—Current Status and Perspectives

Zebrafish avatars: towards functional precision medicine in low-grade serous ovarian cancer

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