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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/29031200/oleanolic-acid-methyl-ester-a-novel-cytotoxic-mitocan-induces-cell-cycle-arrest-and-ros-mediated-cell-death-in-castration-resistant-prostate-cancer-pc-3-cells
#4
Noha Abdelmageed, Samy A F Morad, Ashraf A Elghoneimy, Tatiana Syrovets, Thomas Simmet, Hesham El-Zorba, Hossney A El-Banna, Myles Cabot, Magdy I Abdel-Aziz
Oleanolic acid derivatives exhibit potent anticancer activities against numerous types of cancer. However, the antitumor activity of oleanolic acid methylester (OAME), an oleanolic acid derivative, against prostate cancer has not been studied. Hence, the present work was conducted to study the anticancer activities of OAME. Viability assay showed that treatment of cancer cells with OAME induced a significant cell death in concentration- and time-dependent manner. Of note, OAME displayed a selective cytotoxicity against cancer cells compared to normal epithelial cells...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29030409/clinical-relevance-of-androgen-receptor-alterations-in-prostate-cancer
#5
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/29029019/combined-loss-of-eaf2-and-p53-induces-prostate-carcinogenesis-in-male-mice
#6
Yao Wang, Laura E Pascal, Mingming Zhong, Junkui Ai, Dan Wang, Yifeng Jing, Jan Pilch, Qiong Song, Lora H Rigatti, Lara E Graham, Joel B Nelson, Anil V Parwani, Zhou Wang
Mutations in the p53 tumor suppressor are frequent in patients with castration-resistant prostate cancer but less so in patients with localized disease, and Li-Fraumeni patients with germline p53 mutations do not have an increased incidence of prostate cancer, suggesting that additional molecular and/or genetic changes are required for p53 to promote prostate carcinogenesis. EAF2 is a tumor suppressor that is frequently down-regulated in advanced prostate cancer. Previous studies have suggested that p53 binds to EAF2, providing a potential mechanism for their functional interactions...
September 27, 2017: Endocrinology
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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/29019420/what-role-does-stereotactic-ablative-radiotherapy-have-in-advanced-castrate-resistant-prostate-cancer
#13
Ryan Phillips, Piet Ost, Phuoc T Tran
No abstract text is available yet for this article.
October 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/29017493/enzalutamide-versus-abiraterone-as-a-first-line-endocrine-therapy-for-castration-resistant-prostate-cancer-enable-study-for-pca-a-study-protocol-for-a-multicenter-randomized-phase-iii-trial
#14
Kouji Izumi, Atsushi Mizokami, Mikio Namiki, Shogo Inoue, Nobumichi Tanaka, Yuko Yoshio, Kei Ishibashi, Manabu Kamiyama, Noriyasu Kawai, Hideki Enokida, Takashi Shima, Shizuko Takahara
BACKGROUND: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC...
October 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29017052/cellular-origin-of-androgen-receptor-pathway-independent-prostate-cancer-and-implications-for-therapy
#15
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/28992664/-clinical-study-on-the-efficacy-and-continuous-docetaxel-based-chemotherapy-treatment-for-castration-resistant-prostate-cancer
#16
Ippei Chikazawa, Shinya Inoue, Yusuke Nakazawa, Dan Nakai, Nobuyo Morita, Tatsuro Tanaka, Yoshiharu Motoo, Katsuhito Miyazawa
We report a retrospective study on the efficacy, adverse events and the factors for continuous docetaxel (DOC) therapy for patients with castration-resistant prostate cancer (CRPC). Between April 2007 and April 2015, 37 CRPC patients were treated with DOC therapy at Kanazawa Medical University Hospital. DOC was administered every 3 weeks at 70 mg/m2. Prostatic specific antigen (PSA) level, adverse events, cycles of DOC therapy, survival time and clinical passage were examined. Fifteen patients showed a decrease in PSA level of 50% or more, 9 patients showed less than 50% decrease in PSA level and 13 patients showed no decrease in PSA level...
September 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28991234/dhx15-promotes-prostate-cancer-progression-by-stimulating-siah2-mediated-ubiquitination-of-androgen-receptor
#17
Y Jing, M M Nguyen, D Wang, L E Pascal, W Guo, Y Xu, J Ai, F-M Deng, K Z Masoodi, X Yu, J Zhang, J B Nelson, S Xia, Z Wang
Androgen receptor (AR) activation is critical for prostate cancer (PCa) development and progression, including castration resistance. The nuclear export signal of AR (NES(AR)) has an important role in AR intracellular trafficking and proteasome-dependent degradation. Here, we identified the RNA helicase DHX15 as a novel AR co-activator using a yeast mutagenesis screen and revealed that DHX15 regulates AR activity by modulating E3 ligase Siah2-mediated AR ubiquitination independent of its ATPase activity. DHX15 and Siah2 form a complex with AR, through NES(AR)...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28986618/-177-lu-psma-therapy-current-evidence-for-use-in-the-treatment-of-patients-with-metastatic-prostate-cancer
#18
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/28986367/inhibition-of-p300-cbp-suppresses-castration-resistant-prostate-cancer
#19
(no author information available yet)
A virtual ligand screen led to generation of A-485, a potent selective p300/CBP catalytic inhibitor.
October 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28985240/doxycycline-synergizes-with-doxorubicin-to-inhibit-the-proliferation-of-castration-resistant-prostate-cancer-cells
#20
Chao Zhu, Xueting Yan, Ao Yu, Yongjian Wang
Castration-resistant prostate cancer (CRPC) is fatal and there is currently no effective clinical treatment. The antibiotic doxycycline has shown anti-cancer effect in several kinds of solid tumors including prostate cancer. In this study, a combination of doxycycline and doxorubicin was used to investigate the synergistic effect on CRPC cells. MTT assay was employed to determine the viability of cells in two-dimensional (2D) cultures. Apoptosis was determined by Annexin V/propidium iodide (PI) double staining assay...
September 18, 2017: Acta Biochimica et Biophysica Sinica
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