Forecast cancer: the importance of biomimetic 3D in vitro models in cancer drug testing/discovery and therapy

Caballero, David; Kundu, Banani; Abreu, Catarina M.; Amorim, Sara; Fernandes, Diogo Castro; Oliveira, Joaquím M.; Correlo, Vítor M.; Reis, Rui L.; Kundu, Subhas C.

doi:10.1007/s44164-022-00014-z

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…In this case, the compounds can be organized in multiple layers with well‐defined degradability and release kinetics. [ 19 ]…”

Section: Implantable Cancer Traps For In Vivo Capturing Of Metastatic...mentioning

confidence: 99%

“…In this case, the compounds can be organized in multiple layers with well-defined degradability and release kinetics. [19] Undoubtedly, tumor relapse is a major challenge in cancer treatment, especially in postoperative therapy where bleeding and dispersed tumor cells can lead to recurrence. Cancer traps can help reduce this risk by capturing the remaining cells with the potential of spreading and deliver controlled doses of chemotherapy locally.…”

Section: (Bio)chemical-based Cancer Trapsmentioning

confidence: 99%

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Cancer Traps: Implantable and On‐Chip Solutions for Early Cancer Detection and Treatment

Caballero

Reis

Kundu

2023

Adv Materials Technologies

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Cancer continues to be a major global health issue causing millions of deaths annually. While traditional therapeutic methods may be effective in many cases, they may not be suitable for highly metastatic cancers. Moreover, the late detection of tumors, when they have already spread and are harder to treat, further exacerbates the challenge in managing this disease. As a result, there is a growing interest in developing complementary tissue‐engineered approaches for early cancer diagnosis and treatment to enhance patient recovery. Bioengineered cancer traps have gained significant attention due to their efficacy and ease of use. These trapping systems employ (bio)chemical and mechanical strategies to selectively capture and limit the spread of cancer cells, leading to their eradication from the body. Furthermore, when integrated into microfluidic devices, these cancer traps‐on‐a‐chip can be used for liquid biopsy and the early detection of circulating tumor cells and other tumor‐derived material, allowing for precision medicine treatments. Herein, this innovative approach to cancer theranostics, including its mechanism of action, current stage of development, and potential advantages and limitations is discussed.

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“…In this case, the compounds can be organized in multiple layers with well‐defined degradability and release kinetics. [ 19 ]…”

Section: Implantable Cancer Traps For In Vivo Capturing Of Metastatic...mentioning

confidence: 99%

Section: (Bio)chemical-based Cancer Trapsmentioning

confidence: 99%

Cancer Traps: Implantable and On‐Chip Solutions for Early Cancer Detection and Treatment

Caballero

Reis

Kundu

2023

Adv Materials Technologies

Self Cite

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“…Unfortunately, 95% of new cancer chemotherapeutics fail in clinical trials due to a lack of adequate preclinical models to mimic accurately the TME ex vivo [20][21][22]. Animal models remain a key asset in preclinical drug screening assays as they can recapitulate relevant TME components, but they are expensive, time-consuming, have associated ethical problems, and do not always represent the human TME and its key compartments and components [23,24].…”

Section: Introductionmentioning

confidence: 99%

Multicompartmentalized microvascularized tumor-on-a-chip to study tumor-stroma interactions and drug resistance in ovarian cancer

Plesselova,

Calar,

Axemaker

et al. 2024

Preprint

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IntroductionThe majority of ovarian cancer (OC) patients receiving standard of care chemotherapy develop chemoresistance within 5 years. The tumor microenvironment (TME) is a dynamic and influential player in disease progression and therapeutic response. However, there is a lack of models that allow us to elucidate the compartmentalized nature of TME in a controllable, yet physiologically relevant manner and its critical role in modulating drug resistance.MethodsWe developed a 3D microvascularized multiniche tumor-on-a-chip formed by five chambers (central cancer chamber, flanked by two lateral stromal chambers and two external circulation chambers) to recapitulate OC-TME compartmentalization and study its influence on drug resistance. Stromal chambers included endothelial cells alone or cocultured with normal fibroblasts or cancer-associated fibroblasts (CAF).ResultsThe tumor-on-a-chip recapitulated spatial TME compartmentalization including vessel-like structure, stromal-mediated extracellular matrix (ECM) remodeling, generation of oxygen gradients, and delayed drug diffusion/penetration from the circulation chamber towards the cancer chamber. The cancer chamber mimicked metastasis-like migration and increased drug resistance to carboplatin/paclitaxel treatment in the presence of CAF when compared to normal fibroblasts. CAF-mediated drug resistance was rescued by ECM targeted therapy. Critically, these results demonstrate that cellular crosstalk recreation and spatial organization through compartmentalization are essential to determining the effect of the compartmentalized OC-TME on drug resistance.ConclusionsOur results present a functionally characterized microvascularized multiniche tumor-on-a-chip able to recapitulate TME compartmentalization influencing drug resistance. This technology holds the potential to guide the design of more effective and targeted therapeutic strategies to overcome chemoresistance in OC.

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Multicompartmentalized Microvascularized Tumor-on-a-Chip to Study Tumor-Stroma Interactions and Drug Resistance in Ovarian Cancer

Plesselova,

Calar,

Axemaker

et al. 2024

Cel. Mol. Bioeng.

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Introduction The majority of ovarian cancer (OC) patients receiving standard of care chemotherapy develop chemoresistance within 5 years. The tumor microenvironment (TME) is a dynamic and influential player in disease progression and therapeutic response. However, there is a lack of models that allow us to elucidate the compartmentalized nature of TME in a controllable, yet physiologically relevant manner and its critical role in modulating drug resistance. Methods We developed a 3D microvascularized multiniche tumor-on-a-chip formed by five chambers (central cancer chamber, flanked by two lateral stromal chambers and two external circulation chambers) to recapitulate OC-TME compartmentalization and study its influence on drug resistance. Stromal chambers included endothelial cells alone or cocultured with normal fibroblasts or cancer-associated fibroblasts (CAF). Results The tumor-on-a-chip recapitulated spatial TME compartmentalization including vessel-like structure, stromal-mediated extracellular matrix (ECM) remodeling, generation of oxygen gradients, and delayed drug diffusion/penetration from the circulation chamber towards the cancer chamber. The cancer chamber mimicked metastasis-like migration and increased drug resistance to carboplatin/paclitaxel treatment in the presence of CAF when compared to normal fibroblasts. CAF-mediated drug resistance was rescued by ECM targeted therapy. Critically, these results demonstrate that cellular crosstalk recreation and spatial organization through compartmentalization are essential to determining the effect of the compartmentalized OC-TME on drug resistance. Conclusions Our results present a functionally characterized microvascularized multiniche tumor-on-a-chip able to recapitulate TME compartmentalization influencing drug resistance. This technology holds the potential to guide the design of more effective and targeted therapeutic strategies to overcome chemoresistance in OC.

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Forecast cancer: the importance of biomimetic 3D in vitro models in cancer drug testing/discovery and therapy

Cited by 4 publications

References 19 publications

Cancer Traps: Implantable and On‐Chip Solutions for Early Cancer Detection and Treatment

Cancer Traps: Implantable and On‐Chip Solutions for Early Cancer Detection and Treatment

Multicompartmentalized microvascularized tumor-on-a-chip to study tumor-stroma interactions and drug resistance in ovarian cancer

Multicompartmentalized Microvascularized Tumor-on-a-Chip to Study Tumor-Stroma Interactions and Drug Resistance in Ovarian Cancer

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