Prostate organoids: emerging experimental tools for translational research

Beshiri, Michael L.; Agarwal, Supreet; Yin, Juan Juan; Kelly, Kathleen

doi:10.1172/jci169616

Cited by 18 publications

(10 citation statements)

References 60 publications

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“…Recent studies have described the generation of 3D organoid cultures from normal and neoplastic prostate epithelia from genetically modified mouse models and human patients [ 25 ]. Phenotypic characterisation and the development of genetic modification protocols in these organoid cultures has shown that they represent a robust genetically defined model to study normal and neoplastic prostate biology and response to therapeutic agents [ 26 ]. We have used this system to investigate the driver function of the selected candidate genes to validate the screen we performed.…”

Section: Resultsmentioning

confidence: 99%

Identification of genes that promote PI3K pathway activation and prostate tumour formation

Francis,

Capper,

Rust

et al. 2024

Oncogene

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We have performed a functional in vivo mutagenesis screen to identify genes that, when altered, cooperate with a heterozygous Pten mutation to promote prostate tumour formation. Two genes, Bzw2 and Eif5a2, which have been implicated in the process of protein translation, were selected for further validation. Using prostate organoid models, we show that either Bzw2 downregulation or EIF5A2 overexpression leads to increased organoid size and in vivo prostate growth. We show that both genes impact the PI3K pathway and drive a sustained increase in phospho-AKT expression, with PTEN protein levels reduced in both models. Mechanistic studies reveal that EIF5A2 is directly implicated in PTEN protein translation. Analysis of patient datasets identified EIF5A2 amplifications in many types of human cancer, including the prostate. Human prostate cancer samples in two independent cohorts showed a correlation between increased levels of EIF5A2 and upregulation of a PI3K pathway gene signature. Consistent with this, organoids with high levels of EIF5A2 were sensitive to AKT inhibitors. Our study identified novel genes that promote prostate cancer formation through upregulation of the PI3K pathway, predicting a strategy to treat patients with genetic aberrations in these genes particularly relevant for EIF5A2 amplified tumours.

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Section: Resultsmentioning

confidence: 99%

Identification of genes that promote PI3K pathway activation and prostate tumour formation

Francis,

Capper,

Rust

et al. 2024

Oncogene

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“…[16]. При этом частота успешного создания долгосрочных органоидных культур из опухолей предстательной железы значительно ниже, чем для многих других опухолей [17]. Это говорит о том, что условия культивирования органоидов РПЖ нужно оптимизировать.…”

Section: Discussionunclassified

Optimization of a method for determination of docetaxel sensitivity using prostate cancer organoids

Nikulin,

Silkina,

Razumovskaya

et al. 2024

Onkourologiâ

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Background. Analyzing the sensitivity of patient-derived tumor organoids to anti-cancer medications shows great potential for tailoring personalized treatment plans.Aim. To obtain two prostate tumor organoid cultures, optimize the composition of culture medium, and to evaluatethe efficacy of the chemotherapeutic drug docetaxel using the obtained organoid cultures.Materials and methods. The initial tissue was dissociated using the gentleMACS Octo homogenizer. The obtained cells were cultured in Matrigel with different culture media for selection of the optimal one. Cell viability and growth rates were assessed using the MTS assay.Results. In this study, we successfully obtained two organoid cultures of prostate cancer cells and identified the most effective composition of culture medium. Using a cytotoxic test, it was shown that the obtained organoid cultures of prostate cancer cells had different sensitivity to docetaxel which was reflected in different inhibition of the tumor cell growth rate.Conclusion. The utilization of prostate cancer organoids to determine the best treatment approach is a highly promising experimental technology. Nevertheless, additional research is required before integration of this technology into clinical practice.

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“…Earlier studies conducted by Clevers and colleagues demonstrated a PCa organoid model that was developed through continuous growth and differentiation of prostate luminal epithelial stem cells. This organoid model has been used to study the role of R-spondin, Noggin, and testosterone [8,18]. Prostate-specific modification of intestinal medium and other changes in 3D culture conditions [19] have led to a robust procedure for developing mouse-derived prostate organoids [20].…”

Section: Background and Recent Stage Of Prostate Organoid Culturementioning

confidence: 99%

“…In 2018, Beshiri et al first reported the establishment of a PDX-derived organoid from the LuCaP-PDX mouse model. These PDX-derived organoids were further used for drug screening/development purposes [18,21]. Notably, the LuCaP-PDXs have been well characterized and clinically considered as a cohort of advanced PCa PDXs.…”

Section: Induced-pluripotent Stem Cell (Ipsc)-derived Organoidsmentioning

confidence: 99%

Organoids: An Emerging Precision Medicine Model for Prostate Cancer Research

Waseem,

Wang

2024

IJMS

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Prostate cancer (PCa) has been known as the most prevalent cancer disease and the second leading cause of cancer mortality in men almost all over the globe. There is an urgent need for establishment of PCa models that can recapitulate the progress of genomic landscapes and molecular alterations during development and progression of this disease. Notably, several organoid models have been developed for assessing the complex interaction between PCa and its surrounding microenvironment. In recent years, PCa organoids have been emerged as powerful in vitro 3D model systems that recapitulate the molecular features (such as genomic/epigenomic changes and tumor microenvironment) of PCa metastatic tumors. In addition, application of organoid technology in mechanistic studies (i.e., for understanding cellular/subcellular and molecular alterations) and translational medicine has been recognized as a promising approach for facilitating the development of potential biomarkers and novel therapeutic strategies. In this review, we summarize the application of PCa organoids in the high-throughput screening and establishment of relevant xenografts for developing novel therapeutics for metastatic, castration resistant, and neuroendocrine PCa. These organoid-based studies are expected to expand our knowledge from basic research to clinical applications for PCa diseases. Furthermore, we also highlight the optimization of PCa cultures and establishment of promising 3D organoid models for in vitro and in vivo investigations, ultimately facilitating mechanistic studies and development of novel clinical diagnosis/prognosis and therapies for PCa.

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Prostate organoids: emerging experimental tools for translational research

Cited by 18 publications

References 60 publications

Identification of genes that promote PI3K pathway activation and prostate tumour formation

Identification of genes that promote PI3K pathway activation and prostate tumour formation

Optimization of a method for determination of docetaxel sensitivity using prostate cancer organoids

Organoids: An Emerging Precision Medicine Model for Prostate Cancer Research

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