Abstract 863: Circadian gene expression in metastatic sites and association with survival in metastatic castration-resistant prostate cancer

2021 ◽  
Author(s):  
Benjamin D. Booker ◽  
Konrad H. Stopsack ◽  
Travis A. Gerke ◽  
Kathryn Penny ◽  
Philip W. Kantoff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Circadian Gene ◽  
Castration Resistant ◽  
Metastatic Sites

Abiraterone in patients with metastatic castration-resistant prostate cancer progressing after docetaxel and MDV3100.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
Ecaterina Ileana ◽  
Yohann Loriot ◽  
Laurence Albiges ◽  
Christophe Massard ◽  
Aurore Blesius ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Patient Characteristics ◽  
Preliminary Evidence ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Symptom Response ◽  
Psa Response ◽  
Metastatic Sites

4554 Background: Chemotherapy with docetaxel is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). In patients progressing after docetaxel, both abiraterone and MDV3100 have yielded improved survival for patients with mCRPC. The efficacy of abiraterone in patients pre-treated with MDV 3100 is unknown. Methods: We investigated abiraterone-prednisone in 24 patients with cancer progression after docetaxel followed by MDV3100. All patients received abiraterone 1000 mg/day plus prednisone 10mg/day. Prostate-specific antigen (PSA) response, symptom response, and time to progression were assessed. Results: Patient characteristics were as follows: median age: 74 years (53-84), median PSA: 108 ng/mL (2-2541), metastatic sites: bone: all 24 patients, liver/lung: 6 patients (25%), and lymph nodes : 9 patients (38%). Five patients (21%) had a PSA decrease on abiraterone-prednisone. Three patients (13%) achieved a PSA response, defined as a decrease of >50% in PSA, confirmed after≥ 4 weeks. The duration of PSA response was 2, 3 and 4.5 months. Six patients (29%) had a symptomatic response on the pain score and analgesic consumption was decreased. Treatment was well tolerated. Abiraterone-prednisone was discontinued in one patient due to edema and hypokaliemia. Conclusions: This study shows preliminary evidence that abiraterone-prednisone yields activity in patients with mCRPC pretreated with docetaxel and MDV3100.

Association of CTC detection by AdnaTest with outcome on enzalutamide in chemotherapy-naïve castration-resistant prostate cancer: Exploratory results from PREMIERE—A SOGUG trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5052-5052 ◽  
Author(s):  
Albert Font Pous ◽  
Sergio Vazquez-Estevez ◽  
Aranzazu Gonzalez del Alba ◽  
Begoña Mellado ◽  
Ovidio Fernandez Calvo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Castration Resistant Prostate Cancer ◽  
Exact Test ◽  
Castration Resistant ◽  
Expression Studies ◽  
Psa Response ◽  
Gene Expression Studies

5052 Background: Circulating tumor cells (CTCs) enumeration using CellSearch correlates with clinical outcome in prostate cancer, but is limited for gene expression analysis. AdnaTest ProstateCancer is a commercially available CTC immune-enrichment and PCR-related detection method that allows gene expression studies (Antonarakis E, NEJM 2014). It has demonstrated incremental detection of CTCs in patients with no CTCs identified by CellSearch (Samoila A, ASCO 2013) but needs to be clinically qualified. There is a strong need for studies to assess the association with the clinical outcome in CRPC. Methods: Between February and November 2015, 98 asymptomatic or oligo-symptomatic chemotherapy-naïve mCRPC pts were recruited in 16 institutions. Although initially designed to study the predictive value of TMPRSS2-ETS, data emerging after the trial was initiated led the group to prioritize alternative predefined exploratory biomarkers, including plasma AR (Grande E, ASC0 2017 #) and CTC characterization (Grande E, ESMO 2016). Outcome measures included PSA-PFS (sPFS), radiographic PFS (rPFS) and OS. Cox regression was used for survival analyses and Fisher’s exact test for PSA response. Results: Ninety-eight patients had CTC blood samples available. CTCs were detected at baseline, 12 weeks and progression in 36% (35/98), 27% (26/95) and 78% (32/41), respectively. The CTC conversion rate (positive to negative after 12 w) was 43% (15/35). All CTC conversions had ≥50% decline in PSA (15/15) whereas only 35% (7/20) of pts with persistent CTCs. At first interim analysis, with a median follow-up of 10.6 months, detection of CTCs at baseline was associated with worse sPFS (median, 7.59 m versus NR, HR, 3.67; 95% CI 1.90-7.10; P < 0.001), rPFS (median, 12.9 m versus NR; HR, 7.61; 95% CI, 2.80-20.64; P < 0.001) and OS (medians NR, HR, 9.51; 95% CI, 1.11-81.52; P = 0.0398). CTC positive pts were less likely to have a ≥90% decline in PSA (OR, 2.88; 95% CI, 1.13-7.72; P = 0.02). Conclusions: CTC detection using AdnaTest is associated with an adverse outcome in chemotherapy-naïve asymptomatic or oligo-symptomatic mCRPC pts. Clinical trial information: NCT02288936.

scholarly journals Reactivation of Androgen Receptor–Regulated TMPRSS2:ERG Gene Expression in Castration-Resistant Prostate Cancer

2009 ◽  
Vol 69 (15) ◽  
pp. 6027-6032 ◽  
Author(s):  
Changmeng Cai ◽  
Hongyun Wang ◽  
Youyuan Xu ◽  
Shaoyong Chen ◽  
Steven P. Balk
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals IL1B loss is associated with increased AR activity in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Wisam N. Awadallah ◽  
Jagpreet S. Nanda ◽  
Sarah E. Kohrt ◽  
Magdalena M Grabowska
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Cells ◽  
Marker Gene ◽  
Neuroendocrine Differentiation ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant ◽  
Expression And Activity

Castration-resistant prostate cancer represents a continuum of phenotypes, including tumors with high levels of androgen receptor (AR) expression and activity and those which do not express AR and rely on alternative pathways for survival. The process by which AR-positive prostate cancer cells and tumors lose AR expression and acquire neuroendocrine features is referred to as neuroendocrine differentiation. Numerous therapies and exposures have been demonstrated to induce neuroendocrine differentiation in vitro, including the pro-inflammatory cytokine, interleukin 1 beta (IL-1β), encoded by the gene IL1B. The purpose of our studies was to determine the relationship between the expression and activity of AR in relationship to IL-1β and IL1B in prostate cancer. We performed analysis of de-identified human clinical data and generated prostate cancer cell lines with overexpression or knockout of IL1B. In primary prostate cancer, higher expression of IL1B predicts longer time to biochemical recurrence. In metastatic castration-resistant prostate cancer, IL1B expression is decreased and inversely correlates with AR and AR-target gene expression and AR activity, while positively correlating with the neuroendocrine prostate cancer (NEPC) score and neuroendocrine marker gene expression. In vitro, we report that AR-positive castration-resistant prostate cancer cells (C4-2B, 22Rv1) secrete IL-1β, and knockout of IL1B in these cells results in increased AR activity, in the presence and absence of dihydrotestosterone (DHT). Importantly, knockout of IL1B prevented AR attrition during androgen-deprivation. Taken together, our studies demonstrate that loss of IL1B in AR-positive castration-resistant prostate cancer cells can increase and maintain AR activity in the absence of androgens, suggesting another potential mechanism of high AR activity in castration-resistant prostate cancer.

scholarly journals Gene Expression Alterations during Development of Castration-Resistant Prostate Cancer Are Detected in Circulating Tumor Cells

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 39 ◽  
Author(s):  
Andreas Josefsson ◽  
Karin Larsson ◽  
Eva Freyhult ◽  
Jan-Erik Damber ◽  
Karin Welén
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Progression ◽  
Expression Patterns ◽  
Therapy Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Cancer Specific Survival ◽  
Castration Resistant

Development of castration-resistant prostate cancer (CRPC) is associated with alterations in gene expression involved in steroidogenesis and androgen signaling. This study investigates whether gene expression changes related to CRPC development can be identified in circulating tumor cells (CTCs). Gene expression in paired CTC samples from 29 patients, before androgen deprivation therapy (ADT) and at CRPC relapse, was compared using a panel including 47 genes related to prostate cancer progression on a qPCR platform. Fourteen genes displayed significantly changed gene expression in CTCs at CRPC relapse compared to before start of ADT. The genes with increased expression at CRPC relapse were related to steroidogenesis, AR-signaling, and anti-apoptosis. In contrast, expression of prostate markers was downregulated at CRPC. We also show that midkine (MDK) expression in CTCs from metastatic hormone-sensitive prostate cancer (mHSPC) was associated to short cancer-specific survival (CSS). In conclusion, this study shows that gene expression patterns in CTCs reflect the development of CRPC, and that MDK expression levels in CTCs are prognostic for cancer-specific survival in mHSPC. This study emphasizes the role of CTCs in exploring mechanisms of therapy resistance, as well as a promising biomarker for prognostic and treatment-predictive purposes in advanced mHSPC.

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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