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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]

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: GSE93809 | GEO | 2017/01/19

SECONDARY ACCESSION(S): PRJNA362471

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 [CGH]

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 | GSE93812 | 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

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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.

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