Next generation organoid engineering to replace animals in cancer drug testing

Hockney, Sean; Parker, Jessica; Turner, Jasmin E.; Todd, Xanthea; Todryk, Stephen; Gieling, Roben Ger; Hilgen, Gerrit; Simoes, Davina Camargo Madeira; Pal, Deepali

doi:10.1016/j.bcp.2023.115586

Cited by 11 publications

(4 citation statements)

References 151 publications

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“…Indeed, high-throughput, label-free, live cell imaging of MPS offers the potential to become a foundational tool in future pharmaceutical drug discovery [ 109 ]. In addition, the incorporation of biosensors for readouts in real-time [ 110 , 111 ], as well as the connectors and flow generators in the plates and devices [ 112 , 113 , 114 ], will support the adoption of breast cancer MPS alone or in multi-tissue systems for drug toxicity and efficacy testing in the context of cancer [ 115 , 116 , 117 ].…”

Section: Discussionmentioning

confidence: 99%

Adipose Tissue in Breast Cancer Microphysiological Models to Capture Human Diversity in Preclinical Models

Hamel,

Frazier,

Williams

et al. 2024

IJMS

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Female breast cancer accounts for 15.2% of all new cancer cases in the United States, with a continuing increase in incidence despite efforts to discover new targeted therapies. With an approximate failure rate of 85% for therapies in the early phases of clinical trials, there is a need for more translatable, new preclinical in vitro models that include cellular heterogeneity, extracellular matrix, and human-derived biomaterials. Specifically, adipose tissue and its resident cell populations have been identified as necessary attributes for current preclinical models. Adipose-derived stromal/stem cells (ASCs) and mature adipocytes are a normal part of the breast tissue composition and not only contribute to normal breast physiology but also play a significant role in breast cancer pathophysiology. Given the recognized pro-tumorigenic role of adipocytes in tumor progression, there remains a need to enhance the complexity of current models and account for the contribution of the components that exist within the adipose stromal environment to breast tumorigenesis. This review article captures the current landscape of preclinical breast cancer models with a focus on breast cancer microphysiological system (MPS) models and their counterpart patient-derived xenograft (PDX) models to capture patient diversity as they relate to adipose tissue.

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Section: Discussionmentioning

confidence: 99%

Adipose Tissue in Breast Cancer Microphysiological Models to Capture Human Diversity in Preclinical Models

Hamel,

Frazier,

Williams

et al. 2024

IJMS

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“…Actually, clinical research through organoids represents an approach to directly investigate human diseases, bypassing the need to subject patients to clinical trials or conduct studies on animal models. However, it is crucial to validate organoid tissues in parallel with normal and diseased human tissues to enhance the reliability and accuracy of human disease modeling ( 150 ). This approach could enable a more rapid and ethically responsible transition from preclinical research to clinical practice in pediatric cancer treatment, thus improving the efficacy and safety of therapies offered to pediatric cancer patients.…”

Section: Discussion: Challenges and Opportunitiesmentioning

confidence: 99%

Organoids as a new approach for improving pediatric cancer research

Lampis,

Galardi,

Di Paolo

et al. 2024

Front. Oncol.

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A key challenge in cancer research is the meticulous development of models that faithfully emulates the intricacies of the patient scenario, with emphasis on preserving intra-tumoral heterogeneity and the dynamic milieu of the tumor microenvironment (TME). Organoids emerge as promising tool in new drug development, drug screening and precision medicine. Despite advances in the diagnoses and treatment of pediatric cancers, certain tumor subtypes persist in yielding unfavorable prognoses. Moreover, the prognosis for a significant portion of children experiencing disease relapse is dismal. To improve pediatric outcome many groups are focusing on the development of precision medicine approach. In this review, we summarize the current knowledge about using organoid system as model in preclinical and clinical solid-pediatric cancer. Since organoids retain the pivotal characteristics of primary parent tumors, they exert great potential in discovering novel tumor biomarkers, exploring drug-resistance mechanism and predicting tumor responses to chemotherapy, targeted therapy and immunotherapies. We also examine both the potential opportunities and existing challenges inherent organoids, hoping to point out the direction for future organoid development.

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“…Consequently, organoids have found extensive applications in diverse fields, including disease modelling 144 , drug screening 145 , drug evaluation 146 , toxicity assessment 147 , and cancer research 148 . In September 2022, the U.S. Food and Drug Administration (FDA) issued new guidelines, urging the reduction of animal testing and the adoption of novel technologies as alternatives whenever possible, with organoids having emerged as a high-quality substitute for preclinical animal experiments 138 , 149 . To determine the heterogeneity of organoids, single-cell sequencing has been employed in organoid research.…”

Section: St For Drug Researchmentioning

confidence: 99%

Spatial Transcriptomics: A Powerful Tool in Disease Understanding and Drug Discovery

Cao,

Li,

Cui

et al. 2024

Theranostics

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Recent advancements in modern science have provided robust tools for drug discovery. The rapid development of transcriptome sequencing technologies has given rise to single-cell transcriptomics and single-nucleus transcriptomics, increasing the accuracy of sequencing and accelerating the drug discovery process. With the evolution of single-cell transcriptomics, spatial transcriptomics (ST) technology has emerged as a derivative approach. Spatial transcriptomics has emerged as a hot topic in the field of omics research in recent years; it not only provides information on gene expression levels but also offers spatial information on gene expression. This technology has shown tremendous potential in research on disease understanding and drug discovery. In this article, we introduce the analytical strategies of spatial transcriptomics and review its applications in novel target discovery and drug mechanism unravelling. Moreover, we discuss the current challenges and issues in this research field that need to be addressed. In conclusion, spatial transcriptomics offers a new perspective for drug discovery.

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Next generation organoid engineering to replace animals in cancer drug testing

Cited by 11 publications

References 151 publications

Adipose Tissue in Breast Cancer Microphysiological Models to Capture Human Diversity in Preclinical Models

Adipose Tissue in Breast Cancer Microphysiological Models to Capture Human Diversity in Preclinical Models

Organoids as a new approach for improving pediatric cancer research

Spatial Transcriptomics: A Powerful Tool in Disease Understanding and Drug Discovery

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