Orthotopic and metastatic tumour models in preclinical cancer research

Stribbling, Stephen M.; Beach, Callum; Ryan, Anderson J.

doi:10.1016/j.pharmthera.2024.108631

Cited by 2 publications

References 285 publications

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A Self-Assembling Immune-Featured Osteosarcoma Patient/PDX Derived Organoid Model and Biobank for Personalized Immune Therapy

Mu,

Tao,

Wang

et al. 2024

Preprint

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Osteosarcoma (OS) exhibit intra- and inter-heterogeneity, complicating the exploration of effective therapeutic strategies. Traditionalin vitroandin vivomodels are limited in inheriting biological and genomic heterogeneities of OS patients, even in inheriting the features on tumor microenvironment. The prolonged generation time of current models makes the drug development of OS slow and is not suitable to clinically rapid timing. Here, we introduce methods for generating and biobanking patient/PDX-derived osteosarcoma organoids (OS PD(X)Os) that recapitulate the histological, biological and genomic features of their paired OS patients. OS PD(X)Os can be generated quickly with high reliabilityin vitroor transplanted to immunodeficient mice. We further demonstrate an immune-featured OS PD(X)O (named iOS) model and its method for testing personalized chemotherapy response, personalized immune therapeutic strategy and target drug development, such as a novel PRMT5MTAinhibitor ARPN2169 on MTAP-deleted OS. Our studies show that iOS models maintain many typical features of OS and could be rapidly employed to investigate patient-specific therapeutic strategies. Additionally, our biobank establishes a rich resource for basic, translational and even clinical OS researches.

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A Self-Assembling Immune-Featured Osteosarcoma Patient/PDX Derived Organoid Model and Biobank for Personalized Immune Therapy

Mu,

Tao,

Wang

et al. 2024

Preprint

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Development and Characterization of Syngeneic Orthotopic Transplant Models of Obesity-Responsive Triple-Negative Breast Cancer in C57BL/6J Mice

Carson,

Rädler,

Albright

et al. 2024

Cancers

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Obesity is an established risk and progression factor for triple-negative breast cancer (TNBC), but preclinical studies to delineate the mechanisms underlying the obesity-TNBC link as well as strategies to break that link are constrained by the lack of tumor models syngeneic to obesity-prone mouse strains. C3(1)/SV40 T-antigen (C3-TAg) transgenic mice on an FVB genetic background develop tumors with molecular and pathologic features that closely resemble human TNBC, but FVB mice are resistant to diet-induced obesity (DIO). Herein, we sought to develop transplantable C3-TAg cell lines syngeneic to C57BL/6 mice, an inbred mouse strain that is sensitive to DIO. We backcrossed FVB-Tg(C3-1-TAg)cJeg/JegJ to C57BL/6 mice for ten generations, and spontaneous tumors from those mice were excised and used to generate four clonal cell lines (B6TAg1.02, B6TAg2.03, B6TAg2.10, and B6TAg2.51). We characterized the growth of the four cell lines in both lean and DIO C57BL/6J female mice and performed transcriptomic profiling. Each cell line was readily tumorigenic and had transcriptional profiles that clustered as claudin-low, yet markedly differed from each other in their rate of tumor progression and transcriptomic signatures for key metabolic, immune, and oncogenic signaling pathways. DIO accelerated tumor growth of orthotopically transplanted B6TAg1.02, B6TAg2.03, and B6TAg2.51 cells. Thus, the B6TAg cell lines described herein offer promising and diverse new models to augment the study of DIO-associated TNBC.

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Orthotopic and metastatic tumour models in preclinical cancer research

Cited by 2 publications

References 285 publications

A Self-Assembling Immune-Featured Osteosarcoma Patient/PDX Derived Organoid Model and Biobank for Personalized Immune Therapy

A Self-Assembling Immune-Featured Osteosarcoma Patient/PDX Derived Organoid Model and Biobank for Personalized Immune Therapy

Development and Characterization of Syngeneic Orthotopic Transplant Models of Obesity-Responsive Triple-Negative Breast Cancer in C57BL/6J Mice

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