High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41193 | GEO | 2013/01/12
SECONDARY ACCESSION(S): PRJNA176139
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-01-12 | E-GEOD-41193 | biostudies-arrayexpress
Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 21 xenograft tumors
2013-01-12 | E-GEOD-41188 | biostudies-arrayexpress
Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 22 xenograft tumors
2013-01-12 | E-GEOD-41192 | biostudies-arrayexpress
Project description:Prostate cancer research is hampered by a lack of preclinical models which accurately reproduce clinical heterogeneity. We have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from prostate cancer biopsy tissue, and also new lines from metastatic tissue. The lines retained salient features of the original patient tumors, including histopathological and molecular characteristics. Furthermore, they span major subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of neuroendocrine transdifferentiation. This publicly-available resource provides novel tools for the next-generation of prostate cancer research and therapy development.
2013-01-12 | GSE41192 | GEO
Project description:Prostate cancer research is hampered by a lack of preclinical models which accurately reproduce clinical heterogeneity. We have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from prostate cancer biopsy tissue, and also new lines from metastatic tissue. The lines retained salient features of the original patient tumors, including histopathological and molecular characteristics. Furthermore, they span major subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of neuroendocrine transdifferentiation. This publicly-available resource provides novel tools for the next-generation of prostate cancer research and therapy development.
2013-01-12 | GSE41188 | GEO
Project description:High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development
| PRJNA176139 | ENA
Project description:Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. In an effort to address these shortcomings, there has been a recent increase in the use of patient-derived tumour xenografts (PDTX) engrafted into immune-compromised rodents such as athymic nude or NOD/SCID mice for preclinical modelling. Numerous tumour-specific PDTX models have been established and, importantly, they are biologically stable when passaged in mice in terms of global gene-expression patterns, mutational status, metastatic potential, drug responsiveness and tumour architecture. These characteristics might provide significant improvements over standard cell-line xenograft models. This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.
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Project description:Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a 2-year timeframe, at 89% and 38% efficiency, respectively. Whole-exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs. Early-passage PDXs maintain the genomic and transcriptional profiles of the founder PDX. In vivo treatment with etoposide and platinum (EP) in 30 PDX models demonstrated greater sensitivity in PDXs from EP-naïve patients, and resistance to EP corresponded to increased expression of a MYC gene signature. Finally, serial CTC-derived PDXs generated from an individual patient at multiple time points accurately recapitulated the evolving drug sensitivities of that patient's disease. Collectively, this work highlights the translational potential of this strategy.Significance: Effective translational research utilizing SCLC PDX models requires both efficient generation of models from patients and fidelity of those models in representing patient tumor characteristics. We present approaches for efficient generation of PDXs from both biopsies and CTCs, and demonstrate that these models capture the mutational landscape and functional features of the donor tumors. Cancer Discov; 8(5); 600-15. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 517.
| S-EPMC6369413 | biostudies-literature
Project description:A set of 17 prostate cancer patient-derived xenografts (PDX, Lin et al 2014, Cancer research) was analyzed by mass spectrometry-based proteomics to characterize the effects of castration in vivo, and the proteome differences between NEPC and prostate adenocarcinomas.
2019-09-11 | PXD009636 | Pride
Project description:Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012-2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.
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