Abstract 2433:In vitroandin vivoantitumor activity of the next generation HSP90 inhibitor, AT13387, in both hormone-sensitive and castration-resistant prostate cancer models.

2013 ◽  
Author(s):  
Roberta Ferraldeschi ◽  
Somaieh Hedayat ◽  
Tomoko Smyth ◽  
Nicola Wallis ◽  
John Lyons ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hsp90 Inhibitor ◽  
Next Generation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Cancer Models ◽  
Hormone Sensitive

AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

2018 ◽  
Vol 18 (9) ◽  
pp. 869-876
Author(s):  
Samanta Salvi ◽  
Vincenza Conteduca ◽  
Cristian Lolli ◽  
Sara Testoni ◽  
Valentina Casadio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Clinical Trial Design ◽  
Complete Information ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Cancer ◽  
Hormone Sensitive ◽  
Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

scholarly journals Next-generation androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592097813
Author(s):  
Pernelle Lavaud ◽  
Clément Dumont ◽  
Constance Thibault ◽  
Laurence Albiges ◽  
Giulia Baciarello ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Next Generation ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Recent Advances

Until recently, continuing androgen deprivation therapy (ADT) and closely monitoring patients until evolution towards metastatic castration-resistant prostate cancer (CRPC) were recommended in men with non-metastatic CRPC (nmCRPC). Because delaying the development of metastases and symptoms in these patients is a major issue, several trials have investigated next-generation androgen receptor (AR) axis inhibitors such as apalutamide, darolutamide, and enzalutamide in this setting. This review summarizes the recent advances in the management of nmCRPC, highlighting the favourable impact of next-generation AR inhibitors on metastases-free survival, overall survival and other clinically meaningful endpoints.

scholarly journals Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer

2021 ◽  
Author(s):  
Shotaro Nakanishi ◽  
Masato Goya ◽  
Mitsuyoshi Tamaki ◽  
Takuma Oshiro ◽  
Seiichi Saito
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prostate Specific Antigen ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Predictive Marker ◽  
Castration Resistant Prostate Cancer ◽  
Pretreatment Level ◽  
Castration Resistant ◽  
Hormone Sensitive

Abstract Objective: To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. Results: In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥8 (p = 0.004), an extent of disease value (EOD) of ≥2 (p = 0.004), and a 3-month PSA level >1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. For OS, a 3-month PSA level >1% of the pretreatment level was an independent predictor of time to CRPC (p = 0.004).Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level >1% of the pretreatment level correlated with poor a prognosis.

scholarly journals Huaier Extract Inhibits Prostate Cancer Growth via Targeting AR/AR-V7 Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhengfang Liu ◽  
Cheng Liu ◽  
Keqiang Yan ◽  
Jikai Liu ◽  
Zhiqing Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Nuclear Translocation ◽  
Mrna Levels ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Specific Protease ◽  
Hormone Sensitive

The androgen receptor (AR) plays a pivotal role in prostatic carcinogenesis, and it also affects the transition from hormone sensitive prostate cancer (HSPC) to castration-resistant prostate cancer (CRPC). Particularly, the persistent activation of the androgen receptor and the appearance of androgen receptor splicing variant 7 (AR-V7), could partly explain the failure of androgen deprivation therapy (ADT). In the present study, we reported that huaier extract, derived from officinal fungi, has potent antiproliferative effects in both HSPC and CRPC cells. Mechanistically, huaier extract downregulated both full length AR (AR-FL) and AR-V7 mRNA levels via targeting the SET and MYND domain-containing protein 3 (SMYD3) signaling pathway. Huaier extract also enhanced proteasome-mediated protein degradation of AR-FL and AR-V7 by downregulating proteasome-associated deubiquitinase ubiquitin-specific protease 14 (USP14). Furthermore, huaier extract inhibited AR-FL/AR-V7 transcriptional activity and their nuclear translocation. More importantly, our data demonstrated that huaier extract could re-sensitize enzalutamide-resistant prostate cancer cells to enzalutamide treatment in vitro and in vivo models. Our work revealed that huaier extract could be effective for treatment of prostate cancer either as monotherapy or in combination with enzalutamide.

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

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1908
Author(s):  
Alberto Lapini ◽  
Orazio Caffo ◽  
Giovanni Pappagallo ◽  
Roberto Iacovelli ◽  
Rolando Maria D’Angelillo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Hormonal Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Disease Evolution ◽  
Consensus Document ◽  
Castration Resistant ◽  
The Metabolic Syndrome ◽  
Hormone Sensitive ◽  
Monitoring Protocols

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.

A genomic blood test (NETest) identifies neuroendocrine transformation of prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17511-e17511
Author(s):  
Kambiz Rahbar ◽  
Mark S. Kidd ◽  
Ignat A. Drozdov ◽  
Anna Malczewska ◽  
Lisa Bodei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Marker Gene ◽  
Castration Resistant Prostate Cancer ◽  
Tissue Samples ◽  
Blood Gene Expression ◽  
Castration Resistant ◽  
Hormone Sensitive ◽  
Sensitivity Specificity ◽  
Real Time Information

e17511 Background: Neuroendocrine-like differentiation (NELD) and an aggressive phenotype are key features of castration-resistant prostate cancer (CRPC). Current blood-based biomarkers cannot detect these treatment-refractory variants. Our aim was to evaluate the NETest, a blood-based 51-marker gene neuroendocrine detection tool, as a CRPC-diagnostic versus prostate cancer (PCA). Methods: In silico evaluation: NETest gene identification in the TCGA-PRAD ( n= 500 PCA) and CRPC RNAseq datasets (cBIOPortal: dbGap-phs000909.v.p1, tissue samples: n= 47, including 15 CRPC). Blood gene expression: PCA: n= 50, CRPC: n= 40, hormone-sensitive PCA: n= 75 and benign prostatic hyperplasia (BPH: n= 41). NETest assay: Normalized gene expression, algorithmically assessed and scored: 0-100. Cut-off 20. PSA: ECLIA diagnostic assay: cut-off 4ng/L, > 10ng/ml = actionable value. Statistics: ANOVA, AUROC analyses and sensitivity/specificity metrics. Data is mean±SEM. Results: RNAseq: Two (4%) of the 51 NETest genes were identified in TCGA-PCA. In contrast, all 51 NETest genes (100%) were identified in CRPC tumors. Thirty-three (65%) were detected as upregulated (1.09-1425-fold vs. normal tissue). Blood-PCR: 49/51 (96%) NETest genes detected in CRPC blood. NELD-gene expression was significantly upregulated ( > 2-fold, p< 0.01) in CRPC vs. PCA ( TPH1, PNMA2, SSTR etc). NETest scores were elevated in CRPC (79±2.8) (ANOVA, p< 0.0001) vs. PCA (22±2) and BPH (23±3). The AUC differentiating CRPC from PCA was 0.93 ( p< 0.0001). NETest was elevated in 94% of CRPC vs. 13% PCA and 15% BPH (both p< 0.001). The diagnostic sensitivities and specificities were 94% and 87%, respectively. PSA: PSA was elevated in CRPC (220±372ng/ml). This was different to PCA (14±20ng/ml, p< 0.0001) and BPH (10.3±5.7ng/ml, p< 0.003). The AUC for CRPC vs. PCA/BPH was 0.70 ( p= 0.10). PSA > 10ng/ml occurred in 70% of CRPC, 60% of PCA ( p= NS) and 39% of BPH ( p< 0.05). The AUC for NETest (0.93) was significantly better than PSA (z-statistic: 4.63, p< 0.0001). Conclusions: The NETest is a liquid biopsy that detects neuroendocrine neoplasia genes in the blood and accurately identifies NELD in castration-resistant prostate cancer. We anticipate that the NETest could be used to provide real-time information relevant to the evolving neuroendocrine status of a PCA during therapy.

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