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Enzalutamide resistance

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https://www.readbyqxmd.com/read/28063845/comparative-assessment-of-efficacies-between-2%C3%A2-alternative-therapeutic-sequences-with-novel%C3%A2-androgen-receptor-axis-targeted-agents%C3%A2-in-patients-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#1
Hideaki Miyake, Takuto Hara, Keita Tamura, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Masato Fujisawa
BACKGROUND: The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents in patients with docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively...
December 22, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28063195/first-line-non-cytotoxic-therapy-in-chemotherapy-naive-patients-with-metastatic-castration-resistant-prostate-cancer-a-systematic-review-of-ten-randomised-clinical-trials
#2
REVIEW
Michiel H F Poorthuis, Robin W M Vernooij, R Jeroen A van Moorselaar, Theo M de Reijke
OBJECTIVE: To systematically evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We systematically searched PubMed, EMBASE, and the Cochrane libraries up to March 1, 2016 for peer-reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression-free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated...
January 6, 2017: BJU International
https://www.readbyqxmd.com/read/28059768/sox2-promotes-lineage-plasticity-and-antiandrogen-resistance-in-tp53-and-rb1-deficient-prostate-cancer
#3
Ping Mu, Zeda Zhang, Matteo Benelli, Wouter R Karthaus, Elizabeth Hoover, Chi-Chao Chen, John Wongvipat, Sheng-Yu Ku, Dong Gao, Zhen Cao, Neel Shah, Elizabeth J Adams, Wassim Abida, Philip A Watson, Davide Prandi, Chun-Hao Huang, Elisa de Stanchina, Scott W Lowe, Leigh Ellis, Himisha Beltran, Mark A Rubin, David W Goodrich, Francesca Demichelis, Charles L Sawyers
Some cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. We use in vitro and in vivo human prostate cancer models to show that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR)-dependent luminal epithelial cells to AR-independent basal-like cells. This lineage plasticity is enabled by the loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2, and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression...
January 6, 2017: Science
https://www.readbyqxmd.com/read/28049163/correction-niclosamide-inhibits-androgen-receptor-variants-expression-and-overcomes-enzalutamide-resistance-in-castration-resistant-prostate-cancer
#4
(no author information available yet)
No abstract text is available yet for this article.
January 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28045115/skeletal-related-events-significantly-impact-health-related-quality-of-life-in-metastatic-castration-resistant-prostate-cancer-data-from-prevail-and-affirm-trials
#5
F Saad, C Ivanescu, D Phung, Y Loriot, S Abhyankar, T M Beer, B Tombal, S Holmstrom
BACKGROUND: We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. METHODS: Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments...
January 3, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28034074/does-enzalutamide-really-reduce-the-risk-of-progression-compared-with-bicalutamide-in-patients-with-castration-resistant-prostate-cancer
#6
Mehmet Ali Nahit Şendur, Bülent Yalçın
No abstract text is available yet for this article.
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28034067/enzalutamide-versus-bicalutamide-in-castration-resistant-prostate-cancer-the-strive-trial-there-is-no-significant-reduction-in-death-yet
#7
Jorg Michels
No abstract text is available yet for this article.
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28024400/cheminformatics-modeling-of-adverse-drug-responses-by-clinically-relevant-mutants-of-human-androgen-receptor
#8
Naman Paul, Lavinia A Carabet, Nada Lallous, Takeshi Yamazaki, Martin E Gleave, Paul S Rennie, Artem Cherkasov
The human androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of prostate cancer (PCa). Many forms of castration-resistant prostate cancer (CRPC) still rely on the AR for survival. Currently used antiandrogens face clinical limitations as drug resistance develops in patients over time since they all target the mutation-prone androgen binding site (ABS), where gain-of-function mutations eventually convert antagonists into agonists. With a significant number of reported distinct mutations located across the ABS, it is imperative to develop a prognostic platform which would equip clinicians with prior knowledge and actionable strategies if cases of previously unreported AR mutations are encountered...
December 27, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28003320/post-hoc-analysis-of-japanese-patients-from-the-placebo-controlled-prevail-trial-of-enzalutamide-in-patients-with-chemotherapy-naive-metastatic-castration-resistant-prostate-cancer-updated-results
#9
Go Kimura, Takeshi Ueda
A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis...
December 20, 2016: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27993795/gene-polymorphisms-in-antioxidant-enzymes-correlate-with-the-efficacy-of-androgen-deprivation-therapy-for-prostate-cancer-with-implications-of-oxidative-stress
#10
M Shiota, N Fujimoto, M Itsumi, A Takeuchi, J Inokuchi, K Tatsugami, A Yokomizo, S Kajioka, T Uchiumi, M Eto
BACKGROUND: Oxidative stress mitigated by antioxidant enzymes is thought to be involved in the progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT). This study investigated the association between genetic variations in antioxidant enzymes and the efficacy of ADT as well as its biological background. PATIENTS AND METHODS: The non-synonymous or promoter-locating polymorphisms of antioxidant enzymes were examined as well as the time to CRPC progression and overall survival in 104 and 92 patients treated with ADT for metastatic and non-metastatic prostate cancer, respectively...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27990667/clinical-correlates-of-benefit-from-radium-223-therapy-in-metastatic-castration-resistant-prostate-cancer
#11
Ajjai Alva, Luke Nordquist, Stephanie Daignault, Saby George, Jorge Ramos, Costantine Albany, Sudhir Isharwal, Matthew McDonald, Gregory Campbell, Pongwut Danchaivijitr, Sarah Yentz, Aseem Anand, Evan Y Yu
BACKGROUND: We sought to identify potential clinical variables associated with outcomes after radium-223 therapy in routine practice. METHODS: Consecutive non-trial mCRPC patients who received ≥1 dose of radium dichloride-223 at four academic and one community urology-specific cancer centers from May 2013 to June 2014 were retrospectively identified. Association of baseline and on-therapy clinical variables with number of radium doses received and clinical outcomes including overall survival were analyzed using chi-square statistics, cox proportional hazards, and Kaplan-Meier methods...
December 19, 2016: Prostate
https://www.readbyqxmd.com/read/27981431/adjusting-overall-survival-estimates-after-treatment-switching-a-case-study-in-metastatic-castration-resistant-prostate-cancer
#12
Konstantina Skaltsa, Cristina Ivanescu, Shevani Naidoo, De Phung, Stefan Holmstrom, Nicholas R Latimer
BACKGROUND: If patients in oncology trials receive subsequent therapy, standard intention-to-treat (ITT) analyses may inaccurately estimate the overall survival (OS) effect of the investigational product. In this context, a post-hoc analysis of the phase 3 PREVAIL study was performed with the aim to compare enzalutamide with placebo in terms of OS, adjusting for potential confounding from switching to antineoplastic therapies that are not part of standard metastatic castration-resistant prostate cancer (mCRPC) treatment pathways in some jurisdictions...
December 15, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27979426/nuclear-specific-ar-v7-protein-localization-is-necessary-to-guide-treatment-selection-in-metastatic-castration-resistant-prostate-cancer
#13
Howard I Scher, Ryon P Graf, Nicole A Schreiber, Brigit McLaughlin, David Lu, Jessica Louw, Daniel C Danila, Lyndsey Dugan, Ann Johnson, Glenn Heller, Martin Fleisher, Ryan Dittamore
BACKGROUND: Circulating tumor cells (CTCs) expressing AR-V7 protein localized to the nucleus (nuclear-specific) identify metastatic castration-resistant prostate cancer (mCRPC) patients with improved overall survival (OS) on taxane therapy relative to the androgen receptor signaling inhibitors (ARSi) abiraterone acetate, enzalutamide, and apalutamide. OBJECTIVE: To evaluate if expanding the positivity criteria to include both nuclear and cytoplasmic AR-V7 localization ("nuclear-agnostic") identifies more patients who would benefit from a taxane over an ARSi...
December 12, 2016: European Urology
https://www.readbyqxmd.com/read/27972459/number-needed-to-treat-and-cost-per-clinically-meaningful-outcome-of-enzalutamide-and-abiraterone-acetate-for-the-treatment-of-metastatic-castration-resistant-prostate-cancer-that-failed-androgen-deprivation-therapy-in-brazil
#14
A P Sasse, G Lopes, V Teich, A P Fay, M Abadi, N M Schultz, S Stefani
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27942507/impact-of-enzalutamide-on-patient-related-outcomes-in-metastatic-castration-resistant-prostate-cancer-current-perspectives
#15
REVIEW
Jia Luo, Julie N Graff
Prostate cancer claims the lives of more than 25,000 men in the United States yearly, most from metastatic disease. In the past decade, several new medications have been approved for the treatment of metastatic prostate cancer including the antiandrogen enzalutamide. In addition, there has been mounting interest in evaluating health-related quality of life (QoL) in patients with cancer including new more detailed recommendations released by the Prostate Cancer Working Group 3 on how to evaluate patient-related outcomes in clinical trials...
2016: Research and Reports in Urology
https://www.readbyqxmd.com/read/27915475/how-precisely-can-prostate-cancer-be-managed
#16
REVIEW
Liyan Zhuang, Matthew T Johnson
Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2- ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27909718/enzalutamide-inhibits-proliferation-of-gemcitabine-resistant-bladder-cancer-cells-with-increased-androgen-receptor-expression
#17
Koji Kameyama, Kengo Horie, Kosuke Mizutani, Taku Kato, Yasunori Fujita, Kyojiro Kawakami, Toshio Kojima, Tatsuhiko Miyazaki, Takashi Deguchi, Masafumi Ito
Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27900064/enzalutamide-induced-acute-generalized-exanthematous-pustulosis
#18
Chloé Alberto, Maria Polina Konstantinou, Catherine Martinage, Eline Casassa, Emilie Tournier, Haleh Bagheri, Vincent Sibaud, Loïc Mourey, Juliette Mazereeuw-Hautier, Nicolas Meyer, Carle Paul, Cristina Bulai Livideanu
INTRODUCTION: Enzalutamide (Xtandi®) is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013. OBJECTIVE: We report the first case of acute generalized exanthematous pustulosis (AGEP) induced by enzalutamide. OBSERVATION: A 62-year-old male patient with no significant medical history, was diagnosed in April 2014 with metastatic prostatic adenocarcinoma...
November 13, 2016: Journal of Dermatological Case Reports
https://www.readbyqxmd.com/read/27897170/truncation-and-constitutive-activation-of-the-androgen-receptor-by-diverse-genomic-rearrangements-in-prostate-cancer
#19
Christine Henzler, Yingming Li, Rendong Yang, Terri McBride, Yeung Ho, Cynthia Sprenger, Gang Liu, Ilsa Coleman, Bryce Lakely, Rui Li, Shihong Ma, Sean R Landman, Vipin Kumar, Tae Hyun Hwang, Ganesh V Raj, Celestia S Higano, Colm Morrissey, Peter S Nelson, Stephen R Plymate, Scott M Dehm
Molecularly targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signalling undermines therapeutic efficacy and promotes progression to lethal castration-resistant prostate cancer (CRPC), even when patients are treated with potent second-generation AR-targeted therapies abiraterone and enzalutamide. Here we define diverse AR genomic structural rearrangements (AR-GSRs) as a class of molecular alterations occurring in one third of CRPC-stage tumours...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27892725/investigational-serine-threonine-kinase-inhibitors-against-prostate-cancer-metastases
#20
Claudio Festuccia
Androgen deprivation therapy (ADT) is used as first therapeutic approach in prostate cancer (PCa) although castration resistant disease (CRPC) develops with high frequency. CRPC is the consequence of lack of apoptotic responses to ADT. Alternative targeting of the androgen axis with abiraterone and enzalutamide, as well as taxane-based chemotherapy were used in CRPC. Serine/threonine protein kinases (STKs) regulate different molecular pathways of normal and neoplastic cells and participate to development of CRPC as well as to the progression towards a bone metastatic disease (mCRPC)...
January 2017: Expert Opinion on Investigational Drugs
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