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Metastatic castrate resistant prostate cancer

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https://www.readbyqxmd.com/read/29033099/custirsen-ogx-011-combined-with-cabazitaxel-and-prednisone-versus-cabazitaxel-and-prednisone-alone-in-patients-with-metastatic-castration-resistant-prostate-cancer-previously-treated-with-docetaxel-affinity-a-randomised-open-label-international-phase-3-trial
#1
Tomasz M Beer, Sebastien J Hotte, Fred Saad, Boris Alekseev, Vsevolod Matveev, Aude Fléchon, Gwenaelle Gravis, Florence Joly, Kim N Chi, Zafar Malik, Brent Blumenstein, Patricia S Stewart, Cindy A Jacobs, Karim Fizazi
BACKGROUND: Docetaxel and cabazitaxel improve overall survival compared with mitoxantrone in patients with metastatic castration-resistant prostate cancer. Custirsen (OGX011) is a second generation highly specific antisense oligonucleotide that inhibits the production of clusterin, an antiapoptotic protein that is upregulated in response to chemotherapy and that confers treatment resistance. We aimed to assess whether custirsen in combination with cabazitaxel and prednisone increases overall survival in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel...
October 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29033098/moving-toward-a-precision-medicine-approach-in-metastatic-castration-resistant-prostate-cancer
#2
Rahul Aggarwal
No abstract text is available yet for this article.
October 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29032717/bet-inhibitors-in-metastatic-prostate-cancer-therapeutic-implications-and-rational-drug-combinations
#3
Mark C Markowski, Angelo M De Marzo, Emmanuel S Antonarakis
The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas Covered: We speculate that a combination approach using BET inhibition with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer...
October 16, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29030409/clinical-relevance-of-androgen-receptor-alterations-in-prostate-cancer
#4
REVIEW
Emma Jernberg, Anders Bergh, Pernilla Wikström
Prostate cancer (PC) remains a leading cause of cancer-related deaths among men worldwide, despite continuously improved treatment strategies. Patients with metastatic disease are treated by androgen deprivation therapy (ADT) that with time results in the development of castration-resistant prostate cancer (CRPC) usually established as metastases within bone tissue. The androgen receptor (AR) transcription factor is the main driver of CRPC development and of acquired resistance to drugs given for treatment of CRPC, while a minority of patients have CRPC that is non-AR driven...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29027610/risk-factors-for-and-incidence-of-seizures-in-metastatic-castration-resistant-prostate-cancer-a-real-world-retrospective-cohort-study
#5
Charles Dharmani, Machaon Bonafede, Andrew Krivoshik
BACKGROUND AND OBJECTIVE: This real-world study assessed the prevalence, risk factors for, and incidence of seizures in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Patients with mCRPC were selected from MarketScan Commercial and Medicare Supplemental Databases between 1 January 2009 and 31 July 2012. Prevalence of seizure risk factors were described separately and in combination with other risk factors. Seizure incidence was calculated overall and for each risk factor group...
October 13, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29027195/tspyl-family-regulates-cyp17a1-and-cyp3a4-expression-potential-mechanism-contributing-to-abiraterone-response-in-metastatic-castration-resistant-prostate-cancer
#6
Sisi Qin, Duan Liu, Manish Kohli, Liguo Wang, Peter T Vedell, David W Hillman, Nifang Niu, Jia Yu, Richard M Weinshilboum, Liewei Wang
The testis-specific Y-encoded-like protein (TSPYL) gene family includes TSPYL1 to TSPYL6. We previously reported that TSPYL5 regulates cytochrome P450 (CYP) 19A1 expression. Here, we show that TSPYLs, especially, TSPYL 1, 2 and 4, can regulate the expression of many CYP genes, including CYP17A1, a key enzyme in androgen biosynthesis, and CYP3A4, an enzyme that catalyzes the metabolism of abiraterone, a CYP17 inhibitor. Furthermore, a common TSPYL1 SNP, rs3828743 (G/A) (Pro62Ser), abolishes TSPYL1's ability to suppress CYP3A4 expression, resulting in reduced abiraterone concentrations and increased cell proliferation...
October 13, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29027074/uptake-of-radium-223-dichloride-and-early-18-f-naf-pet-response-are-driven-by-baseline-18-f-naf-parameters-a-pilot-study-in-castration-resistant-prostate-cancer-patients
#7
Arthur Letellier, Alison C Johnson, Nicolas How Kit, Jean-François Savigny, Alain Batalla, Jean-Jacques Parienti, Nicolas Aide
PURPOSE: The purpose of this study is to identify predictive factors on baseline [(18)F]NaF positron emission tomography (PET)/computed tomography (CT) of early response to radium-223 dichloride after 3 cycles of treatment in metastatic castration-resistant prostate cancer patients. PROCEDURES: Analysis of 152 metastases was performed in six consecutive patients who underwent [(18)F]NaF PET/CT at baseline and for early monitoring after 3 cycles of radium-223 dichloride...
October 12, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29026946/psma-targeted-radioligandtherapy-in-metastatic-castration-resistant-prostate-cancer-after-chemotherapy-abiraterone-and-or-enzalutamide-a-retrospective-analysis-of-overall-survival
#8
K Rahbar, M Boegemann, A Yordanova, M Eveslage, M Schäfers, M Essler, H Ahmadzadehfar
AIM: Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with (177)Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer. METHODS: A total of 104 patients were treated with 351 cycles of (177)Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle...
October 12, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29026202/loss-of-abhd5-promotes-the-aggressiveness-of-prostate-cancer-cells
#9
Guohua Chen, Guoli Zhou, Siddhesh Aras, Zhenhui He, Stephanie Lucas, Izabela Podgorski, Wael Skar, James G Granneman, Jian Wang
The accumulation of neutral lipids in intracellular lipid droplets has been associated with the formation and progression of many cancers, including prostate cancer (PCa). Alpha-beta Hydrolase Domain Containing 5 (ABHD5) is a key regulator of intracellular neutral lipids that has been recently identified as a tumor suppressor in colorectal cancer, yet its potential role in PCa has not been investigated. Through mining publicly accessible PCa gene expression datasets, we found that ABHD5 gene expression is markedly decreased in metastatic castration-resistant PCa (mCRPC) samples...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29022046/-radium-223-dichloride-in-patients-with-castration-refractory-prostate-cancer
#10
REVIEW
B M Winter, F-C von Rundstedt, M-O Grimm
Since November 2013, the alpha emitter radium-223 dichloride (Alpharadin/Xofigo®) has been approved for the treatment of men with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. In the ASYMPCA clinical trial, radium-223 was shown to improve overall survival and to reduce the time to the first symptomatic skeletal event. The use of radium-223 was associated with a reduction of pain and an improvement of health-related quality of life compared to the placebo arm...
October 11, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29017052/cellular-origin-of-androgen-receptor-pathway-independent-prostate-cancer-and-implications-for-therapy
#11
W Nathaniel Brennen, John T Isaacs
In this issue of Cancer Cell, Bluemn et al. report that ∼20% of metastatic castration-resistant prostate cancers express neither AR nor neuroendocrine genes and show AR pathway-independent growth, driven instead by a FGFR/MAPK/ID1 signaling cascade. These results provide a strong rationale for co-targeting AR bypass pathways with initial AR antagonism.
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28986618/-177-lu-psma-therapy-current-evidence-for-use-in-the-treatment-of-patients-with-metastatic-prostate-cancer
#12
REVIEW
M Boegemann, A J Schrader, K Rahbar
BACKGROUND: Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and (223)Ra), most of these patients still succumb to prostate cancer. Recently, (177)lutetium prostate-specific membrane antigen radioligand therapy ((177)Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy...
October 6, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28982515/robotic-total-pelvic-exenteration-with-intracorporeal-sigmoid-conduit-and-colostomy-step-by-step-technique
#13
Matthew J Maurice, Daniel Ramirez, Emre Gorgun, Georges-Pascal Haber
OBJECTIVE: To describe our technique for robotic total pelvic exenteration with intracorporeal sigmoid conduit and colostomy using the da Vinci Si robot. METHODS: Three 8-mm robotic ports and two 12-mm laparoscopic ports are placed in a "W" configuration, approximately 2-3 cm more cephalad than for radical prostatectomy (Fig. 1). The robot is docked between the legs with the patient in steep Trendelenburg. The ureters are dissected out from the iliac vessels to the rectovesical pouch, where they are clipped and transected...
July 2017: Urology
https://www.readbyqxmd.com/read/28981098/ap4-modulated-by-the-pi3k-akt-pathway-promotes-prostate-cancer-proliferation-and-metastasis-of-prostate-cancer-via-upregulating-l-plastin
#14
Changhao Chen, Qingqing Cai, Wang He, Thomas B Lam, Jianxun Lin, Yue Zhao, Xu Chen, Peng Gu, Hao Huang, Miaoxin Xue, Hao Liu, Feng Su, Jian Huang, Jianping Zheng, Tianxin Lin
The transition from androgen-dependent to metastatic castration-resistant prostate cancer (PCa) is a lethal event of uncertain molecular aetiology. Our previous studies demonstrated that L-plastin is involved in PCa invasion and metastasis and is upregulated by androgen and oestrogen in the hormone-dependent PCa cell line LNCaP. We recently found that L-plastin expression is consistently activated even after androgen deprivation, suggesting that androgen-independent transcription factors may regulate its expression...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28980045/-the-role-of-psma-pet-ct-in-patients-with-metastatic-prostate-cancer
#15
REVIEW
J von Hardenberg, K-A Büsing, P Nuhn, M Ritter
Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) imaging for the localization of prostate cancer is increasingly available in Germany. The advances and limitations in different disease stages are reviewed. As the clinical relevance of oligometastatic disease in primary cancer detected by PSMA PET-CT imaging is not yet completely understood, it should only be used in clinical trials. In recurrent prostate cancer after therapy with curative intent, PSMA PET-CT shows encouraging potential for the planning of salvage therapy...
October 4, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28978327/abiraterone-acetate-plus-lhrh-therapy-versus-abiraterone-acetate-while-sparing-lhrh-therapy-in-patients-with-progressive-metastatic-and-chemotherapy-na%C3%A3-ve-castration-resistant-prostate-cancer-spare-study-protocol-for-a-randomized-controlled-trial
#16
Carsten-Henning Ohlmann, Michelle Jäschke, Peter Jaehnig, Susane Krege, Jürgen Gschwend, Heidrun Rexer, Michael Stöckle
BACKGROUND: The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible...
October 4, 2017: Trials
https://www.readbyqxmd.com/read/28978108/tunicamycin-induced-endoplasmic-reticulum-stress-promotes-apoptosis-of-prostate-cancer-cells-by-activating-mtorc1
#17
Prasun Guha, Engin Kaptan, Padmaja Gade, Dhananjaya V Kalvakolanu, Hafiz Ahmed
Studies suggest that tunicamycin may work as a therapeutic drug to cancer cells by inducing stress in the endoplasmic reticulum (ER) through unfolded protein response (UPR) and thereby promoting apoptosis. However, mechanisms of the prolonged activation of the UPR under sustained ER stress in the regulation of cell apoptosis are largely unknown. To delineate the role of candidate genes in the apoptotic process under ER stress and to search for new therapeutic strategies to treat metastatic castration resistant prostate cancer, we performed whole genome expression microarray analysis in tunicamycin treated metastatic androgen-insensitive prostate cancer cells, PC-3...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978002/establishment-of-a-neuroendocrine-prostate-cancer-model-driven-by-the-rna-splicing-factor-srrm4
#18
Yinan Li, Ruiqi Chen, Mary Bowden, Fan Mo, Yen-Yi Lin, Martin Gleave, Colin Collins, Xuesen Dong
Neuroendocrine prostate cancer (NEPC) is becoming more prevalent as more potent androgen receptor (AR) pathway inhibitors are applied to patients with metastatic tumors. However, there are limited cell and xenograft models currently available, hindering the investigation of signal pathways involved in regulating NEPC progression and the design of high throughput screening assays for inhibitors to treat NEPC patients. Here, we report an NEPC model, LnNE, that is derived from prostate adenocarcinoma cells and has global similarity in transcription and RNA splicing to tumors from NEPC patients...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977932/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#19
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975586/impact-of-treatment-delay-in-radium-223-therapy-of-metastatic-castration-resistant-prostate-cancer-patients
#20
Marie Øbro Fosbøl, Peter Meidahl Petersen, Gedske Daugaard, Søren Holm, Andreas Kjaer, Jann Mortensen
BACKGROUND: Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities. The aim of this study was to assess whether prolonged interval between Ra-223 cycles to non-disease related causes had a negative impact on clinical outcome of therapy. MATERIALS AND METHODS: Retrospective single-center study of mCRPC patients who initiated Ra-223 therapy in the period from March 2014 to February 2015...
October 3, 2017: Annals of Nuclear Medicine
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