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Abiraterone

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https://www.readbyqxmd.com/read/28924064/circulating-steroid-hormone-variations-throughout-different-stages-of-prostate-cancer
#1
Gido Snaterse, Jenny A Visser, Wiebke Arlt, Johannes Hofland
Steroid hormones play a central role in the maintenance and progression of prostate cancer. The androgen receptor is the primary driver of tumor cell proliferation and is activated by the androgens testosterone and 5α-dihydrotestosterone. Inhibition of this pathway through medical or surgical castration improves survival in the majority of advanced prostate cancer patients. However, conversion of adrenal androgen precursors and alternative steroidogenic pathways have been found to contribute to tumor progression and resistance to treatment...
September 18, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28919099/development-of-an-abiraterone-acetate-formulation-with-improved-oral-bioavailability-guided-by-absorption-modeling-based-on-in-vitro-dissolution-and-permeability-measurements
#2
Tamás Solymosi, Zsolt Ötvös, Réka Angi, Betti Ordasi, Tamás Jordán, Sándor Semsey, László Molnár, Soma Ránky, Genovéva Filipcsei, Gábor Heltovics, Hristos Glavinas
Particle size reduction of drug crystals in the presence of surfactants (often called "top-down" production methods) is a standard approach used in the pharmaceutical industry to improve bioavailability of poorly soluble drugs. Based on the mathematical model used to predict the fraction dose absorbed this formulation approach is successful when dissolution rate is the main rate limiting factor of oral absorption. In case compound solubility is also a major factor this approach might not result in an adequate improvement in bioavailability...
September 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28903426/the-prognostic-implication-of-intraductal-carcinoma-of-the-prostate-in-metastatic-castration-resistant-prostate-cancer-and-its-potential-predictive-value-in-those-treated-with-docetaxel-or-abiraterone-as-first-line-therapy
#3
Jinge Zhao, Pengfei Shen, Guangxi Sun, Ni Chen, Jiandong Liu, Xin Tang, Rui Huang, Diming Cai, Jing Gong, Xingming Zhang, Zhibin Chen, Xiang Li, Qiang Wei, Peng Zhang, Zhenhua Liu, Jiyan Liu, Hao Zeng
Intraductal carcinoma of the prostate (IDC-P) is recognized as a newly pathological entity in 2016 WHO classification. It's role in metastatic castration-resistant prostate cancer (CRPC) remains obscure. We aimed to explore the association of IDC-P with clinical outcome and to further identify its potential predictive role in making first-line treatment decisions for mCRPC. We retrospectively analyzed data of 131 mCRPC patients. IDC-P was diagnosed by re-biopsy at the time of mCRPC. Among total patients, 45 and 41 received abiraterone or docetaxel as first-line therapies, respectively...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903374/resveratrol-enhances-polyubiquitination-mediated-arv7-degradation-in-prostate-cancer-cells
#4
Sarah Wilson, Lucia Cavero, Dali Tong, Qiuli Liu, Kyla Geary, Nicholas Talamonti, Jing Xu, Junjiang Fu, Jun Jiang, Dianzheng Zhang
Although androgen deprivation therapy (ADT) serves as the primary treatment option for localized or metastatic prostate cancer, most cases eventually develop into castration-resistant prostate cancer (CRPC). However, androgen receptor (AR) continues to be functional in CRPC through various mechanisms, including the development of AR splicing variants, especially ARV7. Since it lacks the ligand binding domain but retains the intact DNA binding domain, ARV7 is constitutively active, which makes ARV7-positive prostate cancer responsive to neither abiraterone nor enzalutamide...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893901/expression-of-pd-l1-in-hormone-na%C3%A3-ve-and-treated-prostate-cancer%C3%A2-patients-receiving-neoadjuvant%C3%A2-abiraterone-acetate-plus-prednisone-and-leuprolide
#5
Carla Calagua, Joshua Russo, Yue Sun, Rachel Schaefer, Rosina Lis, Zhenwei Zhang, Kathleen M Mahoney, Glenn J Bubley, Massimo Loda, Mary-Ellen Taplin, Steven P Balk, Huihui Ye
PURPOSE: Programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) blockade has been unsuccessful in prostate cancer (PCa), with poor immunogenicity and subsequent low PD-L1 expression in PCa being proposed as an explanation. However, recent studies indicate that a subset of PCa may express significant levels of PD-L1. Further, the androgen antagonist enzalutamide has been shown to up-regulate PD-L1 expression in PCa preclinical models. In this study, we evaluated the effect of neoadjuvant androgen deprivation therapy with abiraterone acetate plus prednisone and leuprolide (Neo-AAPL) on PD-L1 expression in PCa...
September 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28893623/cyp17a1-inhibitor-abiraterone-an-anti-prostate-cancer-drug-also-inhibits-the-21-hydroxylase-activity-of-cyp21a2
#6
Jana Malikova, Simone Brixius-Anderko, Sameer S Udhane, Shaheena Parween, Bernhard Dick, Rita Bernhardt, Amit V Pandey
Abiraterone is an inhibitor of CYP17A1 which is used for the treatment of castration resistant prostate cancer. Abiraterone is known to inhibit several drug metabolizing cytochrome P450 enzymes including CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, but its effects on steroid metabolizing P450 enzymes are not clear. In preliminary results, we had observed inhibition of CYP21A2 by 1μM abiraterone. Here we are reporting the effect of abiraterone on activities of CYP21A2 in human adrenal cells as well as with purified recombinant CYP21A2...
September 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28890368/cyp17a1-independent-production-of-the-neurosteroid-derived-5%C3%AE-pregnan-3%C3%AE-6%C3%AE-diol-20-one-in-androgen-responsive-prostate-cancer-cell-lines-under-serum-starvation-and-inhibition-by-abiraterone
#7
Antonio G Gomes de Mello Martins, Giuseppe Allegretta, Gerhard Unteregger, Jörg Haupenthal, Jens Eberhard, Michael Hoffmann, Jill A van der Zee, Kerstin Junker, Michael Stöckle, Rolf Müller, Rolf W Hartmann, Carsten-H Ohlmann
CYP17A1-independent intratumoral steroid hormone synthesis is regarded as one possible explanation for resistance to treatment with the CYP17-inhibitor Abiraterone (Abi). The aim of our study was therefore to investigate the steroid metabolism of prostate cancer cells under serum starvation and the effects of Abi treatment. We assessed steroid metabolism in a panel of prostate cancer cells under serum starvation by radioactivity detector-coupled HPLC and HPLC-ESI-ToF-mass spectrometry after treatment with pregnenolone, progesterone and allopregnanolone...
September 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28881288/hydroxytriazole-derivatives-as-potent-and-selective-aldo-keto-reductase-1c3-akr1c3-inhibitors-discovered-by-bioisosteric-scaffold-hopping-approach
#8
Agnese C Pippione, Alessandro Giraudo, Davide Bonanni, Irene M Carnovale, Elisabetta Marini, Clara Cena, Annalisa Costale, Daniele Zonari, Klaus Pors, Maria Sadiq, Donatella Boschi, Simonetta Oliaro-Bosso, Marco L Lolli
The aldo-keto reductase 1C3 isoform (AKR1C3) plays a vital role in the biosynthesis of androgens, making this enzyme an attractive target for castration-resistant prostate cancer therapy. Although AKR1C3 is a promising drug target, no AKR1C3-targeted agent has to date been approved for clinical use. Flufenamic acid, a non-steroidal anti-inflammatory drug, is known to potently inhibit AKR1C3 in a non-selective manner as COX off-target effects are also observed. To diminish off-target effects, we have applied a scaffold hopping strategy replacing the benzoic acid moiety of flufenamic acid with an acidic hydroxyazolecarbonylic scaffold...
August 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28878845/influence-of-androgen-deprivation-therapy-on-the-uptake-of-psma-targeted-agents-emerging-opportunities-and-challenges
#9
REVIEW
Martin K Bakht, So Won Oh, Hyewon Youn, Gi Jeong Cheon, Cheol Kwak, Keon Wook Kang
Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgen-deprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs...
September 2017: Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28874892/treatment-patterns-and-trends-in-patients-dying-of-prostate-cancer-in-quebec-a-population-based-study
#10
A Dragomir, J Rocha, M Vanhuyse, F L Cury, W Kassouf, J Hu, A G Aprikian
INTRODUCTION: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mcrpc) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mcrpc management patterns and therapy utilization trends in Quebec. METHODS: The study cohort consisted of patients dying of prostate cancer (pca) between January 2001 and December 2013, selected from Quebec public health care insurance databases...
August 2017: Current Oncology
https://www.readbyqxmd.com/read/28866822/dutch-economic-value-of-radium-223-in-metastatic-castration-resistant-prostate-cancer
#11
Michel L Peters, Claudine de Meijer, Dirk Wyndaele, Walter Noordzij, Annemarie M Leliveld-Kors, Joan van den Bosch, Pieter H van den Berg, Agni Baka, Jennifer G Gaultney
BACKGROUND: The treatment of metastatic castration-resistant prostate cancer has changed with the introduction of radium-223, cabazitaxel, abiraterone and enzalutamide. To assess value for money, their cost effectiveness in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective was investigated. METHODS: A cost-effectiveness analysis was conducted using efficacy, symptomatic skeletal-related event and safety data obtained from indirect treatment comparisons...
September 2, 2017: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/28866255/novel-junction-specific-and-quantifiable-in-situ-detection-of-ar-v7-and-its-clinical-correlates-in-metastatic-castration-resistant-prostate-cancer
#12
Yezi Zhu, Adam Sharp, Courtney M Anderson, John L Silberstein, Maritza Taylor, Changxue Lu, Pei Zhao, Angelo M De Marzo, Emmanuel S Antonarakis, Mindy Wang, Xingyong Wu, Yuling Luo, Nan Su, Daniel Nava Rodrigues, Ines Figueiredo, Jonathan Welti, Emily Park, Xiao-Jun Ma, Ilsa Coleman, Colm Morrissey, Stephen R Plymate, Peter S Nelson, Johann S de Bono, Jun Luo
BACKGROUND: Androgen receptor splice variant 7 (AR-V7) has been implicated in resistance to abiraterone and enzalutamide treatment in men with metastatic castration-resistant prostate cancer (mCRPC). Tissue- or cell-based in situ detection of AR-V7, however, has been limited by lack of specificity. OBJECTIVE: To address current limitations in precision measurement of AR-V7 by developing a novel junction-specific AR-V7 RNA in situ hybridization (RISH) assay compatible with automated quantification...
August 30, 2017: European Urology
https://www.readbyqxmd.com/read/28857768/treatment-with-abiraterone-in-metastatic-castration-resistant-prostate-cancer-patients-progressing-after-docetaxel-a-retrospective-study
#13
Giuseppe Cicero, Rossella De Luca, Livio Blasi, Alessio Pepe, Carlo Pavone, Alchiede Simonato, Francesco Dieli
The aim of this study was to evaluate abiraterone's efficacy in Italian patients affected with metastatic prostate cancer progressing after treatment with docetaxel. We conducted a retrospective analysis of 60 patients. Prostate-specific antigen (PSA) reduction in serum was the primary endpoint for evaluating the efficacy of abiraterone in combination with prednisone treatment, whereas reduced pain, safety, progression-free survival, response rate, and overall survival (OS) were secondary endpoints. A significant correlation was noticed between PSA response and OS...
August 28, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28855993/treatment-sequence-in-castration-resistant-prostate-cancer-a-retrospective-study-in-the-new-anti-androgen-era
#14
Senji Hoshi, Kenji Numahata, Kunio Ono, Nobuhiro Yasuno, Vladimir Bilim, Kiyotsugu Hoshi, Hiroshi Amemiya, Isoji Sasagawa, Shoichiro Ohta
In recent years, abiraterone acetate (AA) and enzalutamide (EZL) have become available for the treatment of cancer. Prior clinical trials have demonstrated the benefits of these agents in males with castration-resistant prostate cancer (CRPC). The optimal sequencing of available therapies in the context of efficacy and known cross-resistance remains uncertain. Based on the mechanisms of action and accessible clinical data, AA and EZL may be indicated for the early stages of prostate cancer. Until clinical trials are conducted to determine the best treatment sequence, individualized therapy is required for each patient based on the clinicopathological characteristics...
October 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28852974/low-dose-versus-standard-dose-of-corticosteroids-in-the-management-of-adverse-events-of-special-interest-from-abiraterone-acetate-data-from-a-literature-based-meta-analysis
#15
Giandomenico Roviello, Silvia Paola Corona, Daniele Generali
Abiraterone acetate is a CYP-17 inhibitor approved for the treatment of prostate cancer. Abiraterone acetate (AA) therapy is associated with toxicities, including hypokalemia, hypertension, liver function test abnormalities and cardiac events. These adverse events are traditionally managed with a standard dose of corticosteroids. However, preliminary data are available on the use of a lower dose of corticosteroids. The aim of this report is to perform a pooled analysis evaluating the risk ratio (RR) of AA-related adverse events of special interest associated with low or standard dose of corticosteroids...
August 29, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28851578/moving-towards-precision-urologic-oncology-targeting-enzalutamide-resistant-prostate-cancer-and-mutated-forms-of-the-androgen-receptor-using-the-novel-inhibitor-darolutamide-odm-201
#16
Hendrik Borgmann, Nada Lallous, Deniz Ozistanbullu, Eliana Beraldi, Naman Paul, Kush Dalal, Ladan Fazli, Axel Haferkamp, Pascale Lejeune, Artem Cherkasov, Martin E Gleave
Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist with a chemical structure distinctly different from currently approved AR antagonists that targets both wild-type and mutated ligand binding domain variants to inhibit AR nuclear translocation. Here, we evaluate the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer (CRPC) as well as in AR mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide. Darolutamide significantly inhibited cell growth and AR transcriptional activity in enzalutamide-resistant MR49F cells in vitro, and led to decreased tumor volume and serum prostate-specific antigen levels in vivo, prolonging survival in mice bearing enzalutamide-resistant MR49F xenografts...
August 26, 2017: European Urology
https://www.readbyqxmd.com/read/28844792/prognostic-index-model-for-progression-free-survival-in-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer-treated-with-abiraterone-acetate-plus-prednisone
#17
Charles J Ryan, Thian Kheoh, Jinhui Li, Arturo Molina, Peter De Porre, Joan Carles, Eleni Efstathiou, Philip W Kantoff, Peter F A Mulders, Fred Saad, Kim N Chi
BACKGROUND: Radiographic progression-free survival (rPFS) is associated with overall survival (OS) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients. Using readily assessable baseline clinical and laboratory parameters, we developed a prognostic index model for rPFS in chemotherapy-naïve mCRPC patients without visceral disease who were treated with abiraterone acetate plus prednisone. METHODS: Data from the abiraterone acetate plus prednisone arm of COU-AA-302 were used...
July 25, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28844372/antitumour-activity-and-safety-of-enzalutamide-in-patients-with-metastatic-castration-resistant-prostate-cancer-previously-treated-with-abiraterone-acetate-plus-prednisone-for-%C3%A2-24-weeks-in-europe
#18
Johann S de Bono, Simon Chowdhury, Susan Feyerabend, Tony Elliott, Enrique Grande, Amal Melhem-Bertrandt, Benoit Baron, Mohammad Hirmand, Patrick Werbrouck, Karim Fizazi
BACKGROUND: Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported. OBJECTIVE: To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment...
August 22, 2017: European Urology
https://www.readbyqxmd.com/read/28836508/circulating-tumor-cells-and-their-role-in-prostate-cancer
#19
REVIEW
Moritz Maas, Miriam Hegemann, Steffen Rausch, Jens Bedke, Arnulf Stenzl, Tilman Todenhöfer
Circulating tumor cells (CTC) have become an important biomarker in patients with advanced prostate cancer. CTC count has been demonstrated to be a prognostic factor for overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In localized prostate cancer, a clear correlation between CTC counts and clinicopathological risk parameters and outcome has not been observed. Currently, the focus of research is shifting from CTC enumeration towards molecular characterization of CTC leading to the discovery of markers predicting treatment response...
August 22, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28829190/docetaxel-or-abiraterone-in-addition-to-androgen-deprivation-therapy-in-metastatic-castration-sensitive-prostate-cancer
#20
Burak Bilgin, Mehmet An Şendur, Mutlu Hızal, Muhammed Bülent Akıncı, Didem Şener Dede, Bulent Yalçın
No abstract text is available yet for this article.
August 22, 2017: Future Oncology
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