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LuCaP prostate cancer patient-derived xenografts reflect the molecular heterogeneity of advanced disease and serve as models for evaluating cancer therapeutics [CGH]

ABSTRACT: In order to advance our understanding of prostate cancer biology and identify new effective treatments we have established and characterized multiple advanced prostate cancer patient-derived xenografts that mimic well the disease in patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE93812 | GEO | 2017/01/19

SECONDARY ACCESSION(S): PRJNA362470

REPOSITORIES: GEO

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LuCaP prostate cancer patient-derived xenografts reflect the molecular heterogeneity of advanced disease and serve as models for evaluating cancer therapeutics [GE]

Project description:In order to advance our understanding of prostate cancer biology and identify new effective treatments we have established and characterized multiple advanced prostate cancer patient-derived xenografts that mimic well the disease in patients.

2017-01-19 | GSE93809 | GEO

LuCaP Prostate Cancer Patient-Derived Xenografts Reflect the Molecular Heterogeneity of Advanced Disease an--d Serve as Models for Evaluating Cancer Therapeutics.

Project description:BackgroundMetastatic prostate cancer is a common and lethal disease for which there are no therapies that produce cures or long-term durable remissions. Clinically relevant preclinical models are needed to increase our understanding of biology of this malignancy and to evaluate new agents that might provide effective treatment. Our objective was to establish and characterize patient-derived xenografts (PDXs) from advanced prostate cancer (PC) for investigation of biology and evaluation of new treatment modalities.MethodsSamples of advanced PC obtained from primary prostate cancer obtained at surgery or from metastases collected at time of death were implanted into immunocompromised mice to establish PDXs. Established PDXs were propagated in vivo. Genomic, transcriptomic, and STR profiles were generated. Responses to androgen deprivation and docetaxel in vivo were characterized.ResultsWe established multiple PDXs (LuCaP series), which represent the major genomic and phenotypic features of the disease in humans, including amplification of androgen receptor, PTEN deletion, TP53 deletion and mutation, RB1 loss, TMPRSS2-ERG rearrangements, SPOP mutation, hypermutation due to MSH2/MSH6 genomic aberrations, and BRCA2 loss. The PDX models also exhibit variation in intra-tumoral androgen levels. Our in vivo results show heterogeneity of response to androgen deprivation and docetaxel, standard therapies for advanced PC, similar to the responses of patients to these treatments.ConclusionsThe LuCaP PDX series reflects the diverse molecular composition of human castration-resistant PC and allows for hypothesis-driven cause-and-effect studies of mechanisms underlying treatment response and resistance. Prostate 77: 654-671, 2017. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc.

| S-EPMC5354949 | biostudies-literature

LuCaP prostate cancer patient-derived xenografts reflect the molecular heterogeneity of advanced disease and serve as models for evaluating cancer therapeutics

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-01-19 | GSE93808 | GEO

LuCaP prostate cancer patient-derived xenografts reflect the molecular heterogeneity of advanced disease and serve as models for evaluating cancer therapeutics

Project description:LuCaP prostate cancer patient-derived xenografts reflect the molecular heterogeneity of advanced disease and serve as models for evaluating cancer therapeutics

| PRJNA362468 | ENA

RNA seq analysis of LuCaP Prostate Cancer Patient-Derived Xenografts

Project description:We assembled a prostate xenograft interactome from a large data set with 128 RNA sequencing expression profiles generated through administration of 13 small molecule perturbagens in vivo to 5 distinct and genetically diverse LuCaP xenograft lines (LuCaP 73, LuCaP77, LuCaP 78, LuCaP 81, LuCaP 147), with half of the xenograft samples collected from hosts castrated for 1 week.

2023-01-23 | GSE184427 | GEO

RNA seq analysis of LuCaP Prostate Cancer Patient-Derived Xenografts

Project description:RNA seq analysis of LuCaP Prostate Cancer Patient-Derived Xenografts

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Targeted NGS, array-CGH, and patient-derived tumor xenografts for precision medicine in advanced breast cancer: a single-center prospective study.

Project description:BackgroundRoutine feasibility and clinical impact of genomics-based tumor profiling in advanced breast cancer (aBC) remains to be determined. We conducted a pilot study to evaluate whether precision medicine could be prospectively implemented for aBC patients in a single center and to examine whether patient-derived tumor xenografts (PDX) could be obtained in this population.ResultsThirty-four aBC patients were included. Actionable targets were found in 28 patients (82%). A targeted therapy could be proposed to 22 patients (64%), either through a clinical trial (n=15) and/or using already registered drugs (n=21). Ten patients (29%) eventually received targeted treatment, 2 of them deriving clinical benefit. Of 22 patients subjected to mouse implantation, 10 had successful xenografting (45%), mostly in triple-negative aBC.MethodsaBC patients accessible to tumor biopsy were prospectively enrolled at the Institut Paoli-Calmettes in the BC-BIO study (ClinicalTrials.gov, NCT01521676). Genomic profiling was established by whole-genome array comparative genomic hybridization (aCGH) and targeted next-generation sequencing (NGS) of 365 candidate cancer genes. For a subset of patients, a sample of fresh tumor was orthotopically implanted in humanized cleared fat pads of NSG mice for establishing PDX.ConclusionsPrecision medicine can be implemented in a single center in the context of clinical practice and may allow genomic-driven treatment in approximately 30% of aBC patients. PDX may be obtained in a significant fraction of cases.

| S-EPMC5346725 | biostudies-literature

Proteomics of prostate cancer patient derived xenografts

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2019-09-11 | PXD009636 | Pride

Epigenetic landscape of advanced prostate cancer

Project description:Prostate cancer is characterized as being histologically and molecularly heterogeneous. Additionally, epigenetic changes play an important role in regulating the progression of prostate cancer. However, epigenetic intraindividual heterogeneity is largely unknown in advanced prostate cancer. Hence, the epigenetic profiles of advanced prostate cancer, including autopsy cases, were investigated.

2024-07-20 | GSE256194 | GEO

Epigenomic alterations in localized and advanced prostate cancer

Project description:Here we used Illumina NGS for high-throughput profiling of the DNA methylome in seven human benign prostate tissues, seven human primary prostate cancer and six human castration resistant prostate cancer patient samples. These data were used to profile the CpG cytosine methylation pattern at single base resolution in each sample and to determine differentially methylated cytosines and regions among samples. Enhanced Reduced Representation Bisulfite Sequencing (ERRBS, MspI,150M-bM-^@M-^S400 bp size fractions) of 20 human prostate tissues (benign prostate tissues, localized and metastatic prostate cancer)

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