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Patient-derived breast cancer organoid study

ABSTRACT: Patient-derived breast cancer organoid study

PROVIDER: PRJNA786254 | ENA |

REPOSITORIES: ENA

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Patient-derived breast cancer organoid study

Project description:Patient-derived breast cancer organoid study

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Bulk RNA-seq of MilliporeSigma 3DGro human patient-derived gastrointestinal organoid lines compared to SCC300 human iPSC-derived colon organoid line

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DNA methylation analysis of breast cancer patient-derived xenografts and organoids

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several colorectal cancer patient derived tumor organoid RNAseq data

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Mimicking tumor cell heterogeneity of colorectal cancer in a patient-derived organoid-fibroblast model

Project description:Patient derived organoids (PDOs) have been established as a 3D culture model which closely recapitulates the in vivo tumor biology. However, one limitation of this culture model is the lack of tumor microenvironment which has a significant role in tumor progression and drug response. To address this, we established and molecularly characterized a novel 3D co-culture model of colorectal cancer (CRC) based on PDOs and patient matched fibroblasts. Both normal and cancer associated fibroblasts, NFs and CAFs respectively, were able to support organoid growth without addition of niche factors to the media. Additionally, co-cultures showed closer resemblance to primary patient material than organoid mono-cultures as evaluated by histology. Finally, RNA gene expression signatures of tumor cells and fibroblasts isolated from mono- or co-cultures demonstrated that co-cultures support greater cell type heterogeneity. In this proteomics dataset we compared pairs of NFs and CAFs derived from five patients. Collectively, we present a newly established human derived organoid-fibroblast model which, closely recapitulates in vivo tumor heterogeneity and involves the tumor microenvironment.

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Patient-derived response estimates from zero-passage organoids of luminal breast cancer

Project description:Background: Primary luminal breast cancers lose hormone receptors rapidly in standard tissue culture. Breast cancer organoids are thought to retain tumor characteristics better, but long-term viability of luminal-subtype cases is a persistent challenge. Methods: We freshly isolated patient-derived cells from luminal tumor scrapes, miniaturized the organoid format into 5 µl replicates to increase throughput, and set an endpoint of 14 days to minimize drift. Therapeutic hormone targeting was mimicked in these “zero–passage” organoids by withdrawing β-estradiol and adding tamoxifen. We tested sulforaphane as an electrophilic stress and commercial neutraceutical. Genetic perturbations were introduced by lentiviral transduction of two complementary sgRNAs and Cas9 stabilization for the first week of organoid culture. Transcriptional changes were measured by RT-qPCR or RNA sequencing; organoid phenotypes were quantified by serial brightfield imaging, digital image segmentation, and regression modeling of cellular doubling times. Results: We achieved >50% success in initiating luminal breast cancer organoids from tumor scrapes and maintaining them to the 14-day zero-passage endpoint. Few clinical parameters reliably impacted success. Abundance of ESR1 and PGR in zero-passage organoids consistently remained within the range of patient variability at the endpoint. However, responsiveness to hormone withdrawal and blockade was highly variable among luminal breast cancer cases. Combining sulforaphane with knockout of NQO1 (a phase II enzyme) also yielded a breadth of growth phenotypes, including growth inhibition with sulforaphane, growth promotion with NQO1 knockout, and growth antagonism when combined. Conclusions: Zero-passage organoids are a rapid and scalable way to interrogate properties of luminal breast cancer cells from patient-derived material.

2024-03-22 | GSE262110 | GEO

Tumor evolution and drug response in patient-derived organoid models of bladder cancer

Project description:Bladder cancer is the fifth most prevalent cancer in the U.S., yet is understudied and relatively lacking in suitable models. Here we describe a biobank of patient-derived organoid lines that recapitulates the spectrum of human bladder cancer at the histopathological and molecular levels. Organoid lines can be established efficiently from patient biopsies, including from patients before and after disease recurrence, and are interconvertible with orthotopic xenografts. Notably, these organoid lines often retain tumor heterogeneity and exhibit changes in their mutational profiles that are consistent with tumor evolution in culture. Analyses of drug response using bladder tumor organoids show partial correlations with mutational profiles as well as changes associated with treatment resistance, and specific responses can be validated using xenografts in vivo. Overall, our studies indicate that patient-derived bladder tumor organoids represent a model system for studying tumor evolution and treatment response in the context of precision cancer medicine.

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