Establishment and Analysis of Three-Dimensional (3D) Organoids Derived from Patient Prostate Cancer Bone Metastasis Specimens and their Xenografts

Lee, Sanghee; Burner, Danielle; Mendoza, Theresa R; Muldong, Michelle; Arreola, Catalina; Wu, C.; Cacalano, Nicholas A.; Kulidjian, Anna; Kane, Christopher J.; Jamieson, Christina

doi:10.3791/60367

Cited by 15 publications

(16 citation statements)

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“…The cellular heterogeneity of the organoids can be explored using single-cell RNA sequencing[ 63 ]. Instead of primary cultures, some investigators try to create 3D organoids from cancer patient derived xenografts[ 52 , 60 , 64 ].…”

Section: Cancer Samplesmentioning

confidence: 99%

Powerful quantifiers for cancer transcriptomics

Iacobaş

2020

WJCO

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Every day, investigators find a new link between a form of cancer and a particular alteration in the sequence or/and expression level of a key gene, awarding this gene the title of “biomarker”. The clinician may choose from numerous available panels to assess the type of cancer based on the mutation or expression regulation (“transcriptomic signature”) of “driver” genes. However, cancer is not a “one-gene show” and, together with the alleged biomarker, hundreds other genes are found as mutated or/and regulated in cancer samples. Regardless of the platform, a well-designed transcriptomic study produces three independent features for each gene: Average expression level, expression variability and coordination with expression of each other gene. While the average expression level is used in all studies to identify what genes were up-/down-regulated or turn on/off, the other two features are unfairly ignored. We use all three features to quantify the transcriptomic change during the progression of the disease and recovery in response to a treatment. Data from our published microarray experiments on cancer nodules and surrounding normal tissue from surgically removed tumors prove that the transcriptomic topologies are not only different in histopathologically distinct regions of a tumor but also dynamic and unique for each human being. We show also that the most influential genes in cancer nodules [the Gene Master Regulators (GMRs)] are significantly less influential in the normal tissue. As such, “smart” manipulation of the cancer GMRs expression may selectively kill cancer cells with little consequences on the normal ones. Therefore, we strongly recommend a really personalized approach of cancer medicine and present the experimental procedure and the mathematical algorithm to identify the most legitimate targets (GMRs) for gene therapy.

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Section: Cancer Samplesmentioning

confidence: 99%

Powerful quantifiers for cancer transcriptomics

Iacobaş

2020

WJCO

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“…Organoids from primary lung cancer tissues demonstrated the high reproduction levels of histological and genetic characteristics of in situ tissue and their high ability for using them in patient-specific drug trials (Kim et al, 2019). Organoid manner was used for modeling PDAC from patient derived xenografts (PDX) tumors (Nelson et al, 2020) and organoids derived from patient prostate cancer bone metastasis (Lee et al, 2020). Organoids derived from patients with bladder cancer were tested with epirubicin, mitomycin C, gemcitabine, vincristine, doxorubicin, and cisplatin, this model was presented as a prospective model of human bladder cancer (Mullenders et al, 2019; Figure 1C).…”

Section: Three-dimensional Culturesmentioning

confidence: 99%

Cell Culture Based in vitro Test Systems for Anticancer Drug Screening

Kitaeva

Rutland

Rizvanov

et al. 2020

Front. Bioeng. Biotechnol.

109

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The development of new high-tech systems for screening anticancer drugs is one of the main problems of preclinical screening. Poor correlation between preclinical in vitro and in vivo data with clinical trials remains a major concern. The choice of the correct tumor model at the stage of in vitro testing provides reduction in both financial and time costs during later stages due to the timely screening of ineffective agents. In view of the growing incidence of oncology, increasing the pace of the creation, development and testing of new antitumor agents, the improvement and expansion of new high-tech systems for preclinical in vitro screening is becoming very important. The pharmaceutical industry presently relies on several widely used in vitro models, including two-dimensional models, three-dimensional models, microfluidic systems, Boyden's chamber and models created using 3D bioprinting. This review outlines and describes these tumor models including their use in research, in addition to their characteristics. This review therefore gives an insight into in vitro based testing which is of interest to researchers and clinicians from differing fields including pharmacy, preclinical studies and cell biology.

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“…Required additive components differ depending on cell types, gene mutations and phenotypes of PCa. For instance, the addition of 10% FBS helps to promote the proliferation of PCa organoids for patients with bone metastases ( 44 ).…”

Section: Prostate Cancer Organoid Culturesmentioning

confidence: 99%

“…These PDX-organoid models retained the genomic heterogeneity of mCRPC and AR-dependent signaling, thus providing a good platform for the study of the pathogenesis, therapeutic options, and individualized treatment for mCRPC. Furthermore, bone metastatic prostate cancer (BMPC) organoid models derived from patients have been successfully established ( 44 ).…”

Section: Prostate Cancer Organoid Culturesmentioning

confidence: 99%

Application of Organoid Models in Prostate Cancer Research

Zhou

Zhang

et al. 2021

Front. Oncol.

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Complex heterogeneity is an important characteristic in the development of prostate cancer (PCa), which further leads to the failure of known therapeutic options. PCa research has been hampered by the current in vitro model systems that cannot fully reflect the biological characteristics and clinical diversity of PCa. The tumor organoid model in three-dimensional culture retains the heterogeneity of primary tumor tissues in vitro well and enables high-throughput screening and genome editing. Therefore, the establishment of a PCa organoid model that recapitulates the diverse heterogeneity observed in clinical settings is of great significance for the study of PCa. In this review, we summarize the culture conditions, establishments, and limitations of PCa organoids and further review their application for the study of pathogenesis, drug screening, mechanism of drug resistance, and individualized treatment for PCa. Additionally, we look forward to other potential developmental directions of PCa organoids, such as the interaction between prostate cancer tumor cells and their microenvironment, clinical individualized treatments, heterogeneous transformation model, tumor immunotherapy, and organoid models combined with liquid biopsy. Through this, we provide more effective preclinical experimental schemes using the PCa organoid model.

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Establishment and Analysis of Three-Dimensional (3D) Organoids Derived from Patient Prostate Cancer Bone Metastasis Specimens and their Xenografts

Cited by 15 publications

References 0 publications

Powerful quantifiers for cancer transcriptomics

Powerful quantifiers for cancer transcriptomics

Cell Culture Based in vitro Test Systems for Anticancer Drug Screening

Application of Organoid Models in Prostate Cancer Research

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