Down-regulation of ADRB2 expression is associated with small cell neuroendocrine prostate cancer and adverse clinical outcomes in castration-resistant prostate cancer

2020 ◽  
Vol 38 (12) ◽  
pp. 931.e9-931.e16 ◽  
Author(s):  
Daniel H. Kwon ◽  
Li Zhang ◽  
David A. Quigley ◽  
Adam Foye ◽  
William S. Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Small Cell ◽  
Castration Resistant Prostate Cancer ◽  
Down Regulation ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer

scholarly journals Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divya Bhagirath ◽  
Michael Liston ◽  
Theresa Akoto ◽  
Byron Lui ◽  
Barbara A. Bensing ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Neuroendocrine Differentiation ◽  
Extracellular Vesicle ◽  
Machine Learning Algorithms ◽  
Castration Resistant Prostate Cancer ◽  
Cellular Models ◽  
Non Invasive ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer

AbstractNeuroendocrine prostate cancer (NEPC), a highly aggressive variant of castration-resistant prostate cancer (CRPC), often emerges upon treatment with androgen pathway inhibitors, via neuroendocrine differentiation. Currently, NEPC diagnosis is challenging as available markers are not sufficiently specific. Our objective was to identify novel, extracellular vesicles (EV)-based biomarkers for diagnosing NEPC. Towards this, we performed small RNA next generation sequencing in serum EVs isolated from a cohort of CRPC patients with adenocarcinoma characteristics (CRPC-Adeno) vs CRPC-NE and identified significant dysregulation of 182 known and 4 novel miRNAs. We employed machine learning algorithms to develop an ‘EV-miRNA classifier’ that could robustly stratify ‘CRPC-NE’ from ‘CRPC-Adeno’. Examination of protein repertoire of exosomes from NEPC cellular models by mass spectrometry identified thrombospondin 1 (TSP1) as a specific biomarker. In view of our results, we propose that a miRNA panel and TSP1 can be used as novel, non-invasive tools to identify NEPC and guide treatment decisions. In conclusion, our study identifies for the first time, novel non-invasive exosomal/extracellular vesicle based biomarkers for detecting neuroendocrine differentiation in advanced castration resistant prostate cancer patients with important translational implications in clinical management of these patients that is currently extremely challenging.

scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

Evaluation of immunological efficacy of Japanese herbal medicine, hochu-ekki-to and keishi-bukuryo-gan, in patients with castration-resistant prostate cancer under personalized peptide vaccination.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16584-e16584
Author(s):  
Noriko Koga ◽  
Fukuko Moriya ◽  
Kayoko Waki ◽  
Akira Yamada ◽  
Kyogo Itoh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
Clinical Outcomes ◽  
Cytotoxic T Lymphocyte ◽  
Herbal Medicines ◽  
Suppressor Cells ◽  
Human Leukocyte ◽  
Castration Resistant Prostate Cancer ◽  
Peptide Vaccination ◽  
Castration Resistant

e16584 Background: This randomized phase II study investigated the immunological efficacy of herbal medicines (HMs) using Hochu-ekki-to and Keishi-bukuryo-gan, in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Methods: Seventy patients with CRPC were randomly assigned (1:1) to receive PPV plus HMs, or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 peptides derived from cancer antigens according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL), immunoglobulin G (IgG), regulatory T cells (Treg), monocytic myeloid-derived suppressor cells (Mo-MDSC) and interleukin-6 (IL-6) responses were measured before and 8th vaccination. Clinical outcomes were also analyzed. Results: The combination therapy of PPV with HMs was well tolerated without severe adverse events but had no significant impact on antigen-specific IgG and CTL, Treg and clinical outcomes. The combination therapy of PPV with HMs stabilized the frequency of M0-MDSCs (1.91% to 1.92%, p = 0.96) and serum levels of IL-6 (19.2 pg/ml to 16.1 pg/ml, p = 0.63). On the other hand, the frequency of Mo-MDSC and levels of IL-6 in the PPV alone were significantly increased (0.91% to 1.49% for Mo-MDSC and 9.2 pg/ml to 19.4 pg/ml for IL-6, respectively). Conclusions: These results suggested that the combination usage of HMs reveals a potential to prevent the immunosuppression induced by Mo-MDSC or IL-6 during the immunotherapy. More research is needed to validate the findings of the present study. Clinical trial information: 000010290.

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