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https://www.readbyqxmd.com/read/29787892/the-role-of-bisphosphonates-or-denosumab-in-light-of-the-availability-of-new-therapies-for-prostate-cancer
#1
REVIEW
Fred Saad, Cora N Sternberg, Peter F A Mulders, Daniela Niepel, Bertrand F Tombal
Most men with advanced prostate cancer will develop bone metastases, which have a substantial impact on quality of life. Bone metastases can lead to skeletal-related events (SREs), which place a burden on patients and healthcare systems. For men with castration-resistant prostate cancer (CRPC) and bone metastases, the treatment landscape has evolved rapidly over the past few years. The relatively recent approvals of the hormonal agents abiraterone acetate and enzalutamide, second-line chemotherapy cabazitaxel, and the radiopharmaceutical radium-223 dichloride (radium-223), have provided clinicians with a greater choice of treatments...
May 3, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29780751/metastatic-castration-resistant-prostate-cancer-and-the-challenge-of-a-patient-with-chronic-kidney-disease-in-hemodialysis
#2
Joana Simões, Isabel Augusto, Sara Meireles, Lurdes Vendeira, Carlos Silva
At a time when the population shows increasing longevity, entities such as cancer and chronic kidney disease (CKD) are more frequently connected. In the United States, approximately 6% of the patients on hemodialysis have cancer. The challenge to manage oncologic patients with CKD in a hemodialytic program represents a great shortage of available information on the choice of the best drug, timing, dosage adjustments, dialysis method, and treatment safety. We present the case of a patient with prostate cancer and terminal CKD in hemodialysis, and the treatment sequence after the development of resistance to hormonal blockade therapy, which included docetaxel, enzalutamide, and radium-223...
April 2018: Autopsy & Case Reports
https://www.readbyqxmd.com/read/29764892/intense-exercise-for-survival-among-men-with-metastatic-castrate-resistant-prostate-cancer-interval-gap4-a-multicentre-randomised-controlled-phase-iii-study-protocol
#3
Robert U Newton, Stacey A Kenfield, Nicolas H Hart, June M Chan, Kerry S Courneya, James Catto, Stephen P Finn, Rosemary Greenwood, Daniel C Hughes, Lorelei Mucci, Stephen R Plymate, Stephan F E Praet, Emer M Guinan, Erin L Van Blarigan, Orla Casey, Mark Buzza, Sam Gledhill, Li Zhang, Daniel A Galvão, Charles J Ryan, Fred Saad
INTRODUCTION: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS AND ANALYSIS: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC)...
May 14, 2018: BMJ Open
https://www.readbyqxmd.com/read/29760584/lsd1-inhibition-attenuates-androgen-receptor-v7-splice-variant-activation-in-castration-resistant-prostate-cancer-models
#4
Sergio Regufe da Mota, Sarah Bailey, Rosemary A Strivens, Annette L Hayden, Leon R Douglas, Patrick J Duriez, M Teresa Borrello, Hanae Benelkebir, A Ganesan, Graham Packham, Simon J Crabb
Background: Castrate resistant prostate cancer (CRPC) is often driven by constitutively active forms of the androgen receptor such as the V7 splice variant (AR-V7) and commonly becomes resistant to established hormonal therapy strategies such as enzalutamide as a result. The lysine demethylase LSD1 is a co-activator of the wild type androgen receptor and a potential therapeutic target in hormone sensitive prostate cancer. We evaluated whether LSD1 could also be therapeutically targeted in CRPC models driven by AR-V7...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29752180/-177-lu-psma-617-radionuclide-treatment-in-patients-with-metastatic-castration-resistant-prostate-cancer-lupsma-trial-a-single-centre-single-arm-phase-2-study
#5
Michael S Hofman, John Violet, Rodney J Hicks, Justin Ferdinandus, Sue Ping Thang, Tim Akhurst, Amir Iravani, Grace Kong, Aravind Ravi Kumar, Declan G Murphy, Peter Eu, Price Jackson, Mark Scalzo, Scott G Williams, Shahneen Sandhu
BACKGROUND: Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177 Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177 Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments...
May 7, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29748619/eukaryotic-translation-initiation-factor-4-gamma-1-eif4g1-is-upregulated-during-prostate-cancer-progression-and-modulates-cell-growth-and-metastasis
#6
Praveen Kumar Jaiswal, Sweaty Koul, Prakash S T Shanmugam, Hari K Koul
eIF4G1, a critical component of the eIF4F complex, is required for cap-dependent mRNA translation, a process necessary for tumor growth and survival. However, the role of eIF4G1 has not been evaluated in Prostate Cancer (PCa). We observed an increased eIF4G1 protein levels in PCa tissues as compared to normal tissues. Analysis of the TCGA data revealed that eIF4G1 gene expression positively correlated with higher tumor grade and stage. Furthermore, eIF4G1 was over-expressed and or amplified, in 16% patients with metastatic PCa (SU2C/PCF Dream Team dataset) and in 59% of castration-resistant prostate cancer (CRPC) patients (Trento/Cornell/Broad dataset)...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29742084/first-line-use-of-novel-hormonal-agents-in-prostate-cancer-a-critical-appraisal
#7
Derek Raghavan
Castration has been the hallmark of the treatment of advanced prostate cancer for nearly a century. Conventional surgical or medical castration for the management of metastatic prostate cancer has been associated with an initial response rate greater than 60% to 70%, depending on the criteria employed. The median duration of the initial response is usually less than 3 to 5 years, however, depending on the extent of disease. The failure of disease to respond to castration has been associated with an increase in the production of adrenal androgens and/or the evolution of upregulated or mutated androgen receptors...
April 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29731989/statin-use-and-survival-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-abiraterone-or-enzalutamide-after-docetaxel-failure-the-international-retrospective-observational-staben-study
#8
Jacob A Gordon, Carlo Buonerba, Gregory Pond, Daniel Crona, Silke Gillessen, Giuseppe Lucarelli, Sabrina Rossetti, Tanya Dorff, Salvatore Artale, Jennifer A Locke, Davide Bosso, Matthew Ivan Milowsky, Mira Sofie Witek, Michele Battaglia, Sandro Pignata, Cyrus Cherhroudi, Michael E Cox, Pietro De Placido, Dario Ribera, Aurelius Omlin, Gaetano Buonocore, Kim Chi, Christian Kollmannsberger, Daniel Khalaf, Gaetano Facchini, Guru Sonpavde, Sabino De Placido, Bernhard J Eigl, Giuseppe Di Lorenzo
Background: Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes. We investigated the effects of statin use on clinical outcomes in patients with mCRPC receiving abiraterone or enzalutamide. Materials and methods: This was a retrospective multicenter study including patients that received abiraterone or enzalutamide for mCRPC. The effect of concurrent statin use on outcomes was evaluated...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29730201/androgen-receptor-targeted-treatments-for-prostate-cancer-35-years-progress-with-antiandrogens
#9
REVIEW
E David Crawford, Paul F Schellhammer, David G McLeod, Judd W Moul, Celestia S Higano, Neal Shore, Louis Denis, Peter Iversen, Mario A Eisenberger, Fernand Labrie
PURPOSE: Antiandrogens inhibit the androgen receptor (AR) and play an important role in the treatment of prostate cancer (PC). This review provides a historical perspective on the development and clinical benefit of antiandrogens in the treatment of PC. MATERIALS AND METHODS: We searched PubMed® for clinical trials with the search terms "antiandrogens" and "prostate cancer" combined with drug names for antiandrogens. This article represents a collaboration of clinical investigators who have made critical scientific contributions leading to the approval of antiandrogens for treating patients with PC...
May 3, 2018: Journal of Urology
https://www.readbyqxmd.com/read/29700003/inhibition-of-the-wnt-%C3%AE-catenin-pathway-overcomes-resistance-to-enzalutamide-in-castration-resistant-prostate-cancer
#10
Zhuangzhuang Zhang, Lijun Cheng, Jie Li, Elia Farah, Nadia M Atallah, Pete E Pascuzzi, Sanjay Gupta, Xiaoqi Liu
Enzalutamide is a second-generation nonsteroidal antiandrogen clinically approved for the treatment of castration-resistant prostate cancer (CRPC), yet resistance to endocrine therapy has limited its success in this setting. Although the androgen receptor (AR) has been associated with therapy failure, the mechanisms underlying this failure have not been elucidated. Bioinformatics analysis predicted that activation of the Wnt/β-catenin pathway and its interaction with AR play a major role in acquisition of enzalutamide resistance...
April 26, 2018: Cancer Research
https://www.readbyqxmd.com/read/29695920/profile-of-apalutamide-in-the-treatment-of-metastatic-castration-resistant-prostate-cancer-evidence-to-date
#11
REVIEW
Julio T Chong, William K Oh, Bobby C Liaw
Advances in therapies have led to the approval of six therapeutic agents since 2004, each demonstrating overall survival benefit in randomized studies, and these have significantly improved the outlook for men facing metastatic castration-resistant prostate cancer (CRPC). More recently, efforts have been directed at trying to effect change at earlier phases of the disease. Apalutamide (ARN-509), a second-generation androgen receptor antagonist, recently received approval in the nonmetastatic (M0) CRPC space...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29688882/withdrawn-disparity-in-public-funding-of-therapies-for-metastatic-castrate-resistant-prostate-cancer-across-canadian-provinces
#12
Dixon T S Woon, Thenappan Chandrasekar, Lorne Aaron, Naveen S Basappa, Kim N Chi, Henry J Conter, Brita Danielson, Sebastien J Hotte, Shawn Malone, Fred Saad, Bobby Shayegan, Laura Park-Wyllie, Robert J Hamilton
Ahead of print article withdrawn by publisher.
April 12, 2018: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29682197/synthesis-and-anticancer-activity-of-the-derivatives-of-marine-compound-rhizochalin-in-castration-resistant-prostate-cancer
#13
Sergey A Dyshlovoy, Katharina Otte, Kseniya M Tabakmakher, Jessica Hauschild, Tatyana N Makarieva, Larisa K Shubina, Sergey N Fedorov, Carsten Bokemeyer, Valentin A Stonik, Gunhild von Amsberg
Development of resistance to standard therapies complicates treatment of advanced prostate cancer. Alternative splicing variants of the androgen receptor (AR), e.g. AR-V7 can mediate resistance to AR-targeting substances abiraterone and enzalutamide. Semi-synthetic marine natural compound rhizochalinin decreases the expression of AR-V7 in human castration-resistant prostate cancer cells and thus resensitizes cells to enzalutamide. In the current study, we modified the structure of rhizochalin in order to determine structure-activity relationships (SAR) and optimize anticancer properties...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29682196/testosterone-metabolites-inhibit-proliferation-of-castration-and-therapy-resistant-prostate-cancer
#14
Felix Bremmer, Hubertus Jarry, Valerie Unterkircher, Silke Kaulfuss, Peter Burfeind, Heinz-Joachim Radzun, Philipp Ströbel, Paul Thelen
Novel treatments for castration-resistant prostate cancer (CRPC) such as abiraterone acetate (AA) or enzalutamide effectively target the androgen pathway to arrest aberrant signalling and cell proliferation. Testosterone is able to inhibit tumour cell growth in CRPC. Estrogen receptor-beta (ERβ) binds the testosterone-metabolites 3β-androstanediol and 3α-androstanediol in parallel to the canonical estradiol. In the prostate it is widely accepted that ERβ regulates estrogen signalling, mediating anti-proliferative effects...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#15
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29658567/hepacam-inhibits-the-malignant-behavior-of-castration-resistant-prostate-cancer-cells-by-downregulating-notch-signaling-and-pf-3084014-a-%C3%AE-secretase-inhibitor-partly-reverses-the-resistance-of-refractory-prostate-cancer-to-docetaxel-and-enzalutamide-in-vitro
#16
Zhongbo Du, Luo Li, Wei Sun, Xiao Wang, Yao Zhang, Zhixiong Chen, Mengjuan Yuan, Zhen Quan, Nanjing Liu, Yanni Hao, Ting Li, Jinhua Wang, Chunli Luo, Xiaohou Wu
Castration-resistant prostate cancer (CRPC) continues to be a major challenge in the treatment of prostate cancer (PCa). The expression of hepatocyte cell adhesion molecule (HepaCAM), a novel tumor suppressor, is frequently downregulated or lost in PCa. Overactivated Notch signaling is involved in the development and progression of PCa, including CRPC. In this study, we found that the activities of Notch signaling were elevated, while HepaCAM expression was decreased in CRPC tissues compared with matched primary prostate cancer (PPC) tissues...
April 12, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29651807/editorial-comment-to-influence-of-prior-oral-ethinylestradiol-use-on-the-efficacy-of-enzalutamide-for-the-treatment-of-castration-resistant-prostate-cancer-in-men
#17
Kouji Izumi
No abstract text is available yet for this article.
April 12, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29627574/exosomes-secreted-by-placental-stem-cells-selectively-inhibit-growth-of-aggressive-prostate-cancer-cells
#18
Taylor C Peak, Prakash Praharaj, Gati K Panigrahi, Michael Doyle, Yixin Su, Isabel R Schlaepfer, Ravi Singh, Donald J Vander Griend, Julie Alickson, Ashok Hemal, Anthony Atala, Gagan Deep
The current paradigm in the development of new cancer therapies is the ability to target tumor cells while avoiding harm to noncancerous cells. Furthermore, there is a need to develop novel therapeutic options against drug-resistant cancer cells. Herein, we characterized the placental-derived stem cell (PLSC) exosomes (PLSCExo ) and evaluated their anti-cancer efficacy in prostate cancer (PCa) cell lines. Nanoparticle tracking analyses revealed the size distribution (average size 131.4 ± 0.9 nm) and concentration of exosomes (5...
April 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29623850/treatment-of-metastatic-castration-resistant-docetaxel-resistant-prostate-cancer-a-systematic-review-of-literature-with-a-network-meta-analysis-of-randomized-clinical-trials
#19
Davide Tassinari, Chiara Cherubini, Britt Roudnas, Emiliano Tamburini, Fabrizio Drudi, Emanuela Bianchi, Manuela Fantini, Francesco Montanari, Sergio Sartori
INTRODUCTION: To compare the efficacy of abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 in the treatment of castration-resistant, docetaxel-resistant metastatic prostate cancer. METHODS: An indirect comparison of overall survival (OS) and time to PSA progression among abiraterone acetate, enzalutamide, cabazitaxel and Radium-223 was performed with a network meta-analysis. OS in the entire population of patients was the primary end point. OS in ECOG 0-1/2, BPI-SF≤4/>4, pretreated with 1 or 2 courses of chemotherapy, age≤65/>65 patients, patients with only bone metastases or bone and visceral metastases, and time to PSA progression were the secondary end points...
April 4, 2018: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/29621897/current-and-potential-targets-for-drug-design-in-the-androgen-receptor-pathway-for-prostate-cancer
#20
Achuta Kumar Guddati
Modulating the androgen axis by different agents has been one of the most successful therapeutic interventions in the field of prostate cancer therapy. Newer agents such as abiraterone and enzalutamide have been widely adapted and have contributed to an increase in the overall survival of prostate cancer patients. However, most of these patients will develop resistance to these agents and will need chemotherapy. Areas covered: In this review, this author discusses current agents which modulate the androgen axis, the mechanisms of resistance to these agents and investigative agents which are designed to bypass these mechanisms of resistance...
April 6, 2018: Expert Opinion on Drug Discovery
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