Disrupting YAP1-mediated glutamine metabolism induces synthetic lethality alongside ODC1 inhibition in osteosarcoma

Wang, Hongsheng; Tao, Yining; Han, Jing; Shen, Jiakang; Mu, Haoran; Wang, Zhuoying; Wang, Jinzeng; Jin, Xinmeng; Zhang, Qi; Yang, Yuqin; Lin, Jun; Sun, Mengxiong; Ma, Xiaojun; Ren, Ling; LeBlanc, Amy K.; Xu, Jing; Hua, Yingqi; Sun, Wei

doi:10.1007/s13402-024-00967-1

Cell Oncol.

2024

DOI: 10.1007/s13402-024-00967-1

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Disrupting YAP1-mediated glutamine metabolism induces synthetic lethality alongside ODC1 inhibition in osteosarcoma

Hongsheng Wang,

Yining Tao,

Jing Han

et al.

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2024

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Cited by 1 publication

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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

View full text Add to dashboard Cite

show abstract

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Disrupting YAP1-mediated glutamine metabolism induces synthetic lethality alongside ODC1 inhibition in osteosarcoma

Cited by 1 publication

References 54 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

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