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Comparison of the RB loss-induced transcrptiome in hormone-therapy sensitive and castration-resistant prostate cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE154192 | GEO | 2021/04/26

REPOSITORIES: GEO

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Comparison of the RB loss-induced transcrptiome in hormone-therapy sensitive and castration-resistant prostate cancer [RNA-seq]

Project description:These studies examine the biological networks altered after RB loss across prostate cancer progression.

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Comparison of the RB loss-induced E2F1 cistrome in hormone-therapy sensitive and castration-resistant prostate cancer [ChIP-seq]

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Comparison of the RB loss-induced transcrptiome in hormone-therapy sensitive and castration-resistant prostate cancer

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Comparison of the RB loss-induced transcrptiome in hormone-therapy sensitive and castration-resistant prostate cancer [RNA-seq]

Project description:Comparison of the RB loss-induced transcrptiome in hormone-therapy sensitive and castration-resistant prostate cancer [RNA-seq]

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Comparison of the RB loss-induced E2F1 cistrome in hormone-therapy sensitive and castration-resistant prostate cancer [ChIP-seq]

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Hormonal therapy and chemotherapy in hormone-naive and castration resistant prostate cancer.

Project description:The management of advanced castration resistant prostate cancer (CRPC) has been rapidly changing and is still evolving. In the last years, there has been an increasing knowledge of prostate cancer biology. New therapeutic agents and approaches have been evaluated demonstrating benefits in survival and quality of life in patients with metastatic prostate cancer.

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Monitoring Patients with Metastatic Hormone-Sensitive and Metastatic Castration-Resistant Prostate Cancer: A Multidisciplinary Consensus Document.

Project description:BACKGROUND:The availability of a number of agents that are efficacious in patients with metastatic prostate cancer (mPC) has led to them being used sequentially, and this has prolonged patient survival. However, in order to maximize their efficacy, clinicians need to be able to obtain a reliable picture of disease evolution by means of monitoring procedures. METHODS:As the intensive monitoring protocols used in pivotal trials cannot be adopted in everyday clinical practice and there is no agreement among the available guidelines, a multidisciplinary panel of Italian experts met to develop recommendations for monitoring mPC patients using a modified Delphi method. RESULTS:The consensus project considered methods of clinically, radiographically, and biochemically monitoring patients with metastatic hormone-sensitive and metastatic castration-resistant prostate cancer undergoing chemotherapy and/or hormonal treatment. The panelists also considered the methods and timing of monitoring castration levels, bone health, and the metabolic syndrome during androgen deprivation therapy. CONCLUSIONS:The recommendations, which were drawn up by experts following a formal and validated consensus procedure, will help clinicians face the everyday challenges of monitoring metastatic prostate cancer patients.

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Identifying Patients With Rapid Progression From Hormone-Sensitive to Castration-Resistant Prostate Cancer: A Retrospective Study.

Project description:Prostate cancer (PCa) is the second most prevalent malignancy and the fifth cause of cancer-related deaths in men. A crucial challenge is identifying the population at risk of rapid progression from hormone-sensitive prostate cancer (HSPC) to lethal castration-resistant prostate cancer (CRPC). We collected 78 HSPC biopsies and measured their proteomes using pressure cycling technology and a pulsed data-independent acquisition pipeline. We quantified 7355 proteins using these HSPC biopsies. A total of 251 proteins showed differential expression between patients with a long- or short-term progression to CRPC. Using a random forest model, we identified seven proteins that significantly discriminated long- from short-term progression patients, which were used to classify PCa patients with an area under the curve of 0.873. Next, one clinical feature (Gleason sum) and two proteins (BGN and MAPK11) were found to be significantly associated with rapid disease progression. A nomogram model using these three features was generated for stratifying patients into groups with significant progression differences (p-value = 1.3×10-4). To conclude, we identified proteins associated with a fast progression to CRPC and an unfavorable prognosis. Based on these proteins, our machine learning and nomogram models stratified HSPC into high- and low-risk groups and predicted their prognoses. These models may aid clinicians in predicting the progression of patients, guiding individualized clinical management and decisions.

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Bruceantin targets HSP90 to overcome resistance to hormone therapy in castration-resistant prostate cancer.

Project description:Rationale: Aberrant androgen receptor (AR) signaling via full-length AR (AR-FL) and constitutively active AR variant 7 (AR-V7) plays a key role in the development of castration-resistant prostate cancer (CRPC) and resistance to hormone therapies. Simultaneous targeting of AR-FL and AR-V7 may be a promising strategy to overcome resistance to hormone therapy. This study aimed to identify novel drug candidates co-targeting AR-FL and AR-V7 activities and elucidate their molecular mechanism of anti-CRPC activities. Methods: Using a CRPC cell-based reporter assay system, we screened a small library of antimalarial agents to explore the possibility of repositioning them for CRPC treatment and identified bruceantin (BCT) as a potent anti-CRPC drug candidate. A series of cell-based, molecular, biochemical, and in vivo approaches were performed to evaluate the therapeutic potential and molecular mechanism of BCT in CRPC. These approaches include reporter gene assays, cell proliferation, RNA-seq, qRT-PCR, mouse xenografts, co-immunoprecipitation, GST pull-down, immobilized BCT pull-down, molecular modeling, and bioinformatic analyses. Results: We identified BCT as a highly potent inhibitor co-targeting AR-FL and AR-V7 activity. BCT inhibits the transcriptional activity of AR-FL/AR-V7 and downregulates their target genes in CRPC cells. In addition, BCT efficiently suppresses tumor growth and metastasis of CRPC cells. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7 by directly binding to HSP90 and inhibits HSP90 chaperone function, leading to degradation of AR-FL/AR-V7 through the ubiquitin-proteasome system. Clinically, HSP90 expression is upregulated and correlated with AR/AR-V7 levels in CRPC. Conclusion: Our findings suggest that BCT could serve as a promising therapeutic candidate against CRPC and highlight the potential benefit of targeting AR-FL/AR-V7-HSP90 axis to overcome resistance caused by aberrant AR-FL/AR-V7 signaling.

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Identifying the patients with rapid progression from hormone-sensitive to castration-resistant prostate cancer

Project description:We collected 78 biopsies and analyzed the proteomic expression by pressure cycling technology and Pulsed data-independent acquisition (PCT-PulseDIA) pipeline. Next, we explore the differentially expressed proteins (DEPs) in the discovery set (n=16) which contains short (S, n=8)- and long (L, n=8)- term progression. The progression-related proteins were further identified in another dataset, modeling set (n=62), utilizing the ANOVA estimation and random forest model. Multivariable Cox regression analysis was then conducted to determine clinical and protein variables significantly associated with the progression of HSPC in the whole sample set (n=78).

2022-11-04 | PXD037951 |

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