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Enzalutamide resistance

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https://www.readbyqxmd.com/read/28736322/clinical-outcomes-of-chemotherapy-na%C3%A3-ve-men-with-metastatic-castration-resistant-prostate-cancer-and-low-baseline-psa-treated-with-enzalutamide-vs-placebo
#1
Mary-Ellen Taplin, Andrew J Armstrong, Ping Lin, Andrew Krivoshik, De Phung, Teresa Parli, Bertrand Tombal, Tomasz M Beer
PURPOSE: Metastatic castration-resistant prostate cancer with low baseline prostate-specific antigen represents an early stage in the natural history of castration-resistant prostate cancer disease progression (low-volume disease), low prostate-specific antigen-producing disease, or disease less dependent on androgen receptor biology (high-volume disease). We analyzed outcomes in men with low prostate-specific antigen and high disease burden who received the oral androgen-receptor inhibitor enzalutamide in the PREVAIL study...
July 20, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28734596/developments-in-urologic-oncology-%C3%A2-oncoforum%C3%A2-the-best-of-2016
#2
F Gómez-Veiga, A Alcaraz-Asensio, J Burgos-Revilla, J M Cózar-Olmo
OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2016 in the main annual meetings. ACQUISITION OF EVIDENCE: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. SYNTHESIS OF EVIDENCE: In High-Risk Renal-Cell carcinoma after nephrectomy, disease-free survival was significantly greater for sunitinib than placebo group, with adverse events more frequents...
July 19, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/28729398/quercetin-targets-hnrnpa1-to-overcome-enzalutamide-resistance-in-prostate-cancer-cells
#3
Ramakumar Tummala, Wei Lou, Allen C Gao, Nagalakshmi Nadiminty
Prostate cancer remains dependent on androgen receptor signaling even after castration. Aberrant androgen receptor signaling in castration resistant prostate cancer is mediated by mechanisms such as alterations in the androgen receptor and activation of interacting signaling pathways. Clinical evidence confirms that resistance to the next generation anti-androgen, enzalutamide, may be mediated to a large extent by alternative splicing of the androgen receptor to generate constitutively active splice variants such as AR-V7...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28723508/targeting-adaptive-pathways-in-metastatic-treatment-resistant-prostate-cancer-update-on-the-stand-up-2-cancer-prostate-cancer-foundation-supported-west-coast-prostate-cancer-dream-team
#4
Rahul Aggarwal, Tomasz M Beer, Martin Gleave, Joshua M Stuart, Matthew Rettig, Christopher P Evans, Jack Youngren, Joshi J Alumkal, Jiaoti Huang, George Thomas, Owen Witte, Eric J Small
The Stand Up 2 Cancer/Prostate Cancer Foundation-funded West Coast Dream Team project is a prospective multi-institutional study focused on acquiring metastatic castration-resistant prostate cancer (mCRPC) biopsy tissue at the time of resistance to abiraterone or enzalutamide. It is the first large-scale study designed to analyze mCRPC tissue specifically in this patient population. Study accrual is on target, with 261 out of a planned 300 metastatic tumor biopsies performed by August 2016. Paired biopsies have been completed in 42 patients, with paired genomic data before and after therapy obtained in 26 cases...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723476/charting-recent-progress-and-challenges-in-metastatic-castration-resistant-prostate-cancer-is-there-an-optimal-treatment-sequence
#5
REVIEW
Stéphane Oudard, Pablo Maroto, Gaston Demonty, Winald R Gerritsen
CONTEXT: Recent developments in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have led to uncertainty about the optimal sequence of agents. OBJECTIVE: To review and assess treatment options and sequence in patients with mCRPC. EVIDENCE ACQUISITION: To identify data on the optimal use of approved treatments, we searched PubMed for studies on the use of recently approved agents for men with mCRPC published before March 2015...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28711312/radium-223-in-the-therapeutic-sequence-of-metastatic-castration-resistant-prostate-cancer
#6
M Unda-Urzaiz, R Sousa-Campo, A Rodríguez-Antolín, C Silva-Marins, A Juárez-Soto, B Miñana-López, A Figueiredo-de Castro, J M Cozar-Olmos
CONTEXT: Radium-223 is an □ -particle transmitter with specific action on bone metastases. The Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) study showed that radium-223 extended overall survival and delayed the onset of bone events in patients with symptomatic castration-resistant prostate cancer with bone metastases (mCRPC) and without visceral metastases, with a good safety profile. OBJECTIVE: To review the new scientific evidence on radium-223 based on prespecified and post-hoc analyses of the ALSYMPCA study and on early-access programs after the publication of the ALSYMPCA study, thereby providing new data on the management of patients with mCRPC...
July 12, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/28707844/castration-resistance-prostate-cancer-what-is-in-the-pipeline
#7
Cosimo DE Nunzio, Fabrizio Presicce, Silvana Giacinti, Maria Bassanelli, Andrea Tubaro
INTRODUCTION: To evaluate the available evidence on the standard diagnosis and management of men with metastatic castration resistant prostate cancer (mCRPC), and providing the timely update on new pharmacological treatments. EVIDENCE ACQUISITION: A systematic literature search from from January 2000 until March 2017 was performed by combining the following MESH terms: castrate resistant prostate cancer, abiraterone, enzalutamide, 223radium, sipuleucel-T, docetaxel, cabazitaxel, resistance mechanisms, resistance to androgen deprivation, Androgen Receptor (AR) mutations, amplifications, splice variants, and AR alterations...
July 12, 2017: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/28700990/oncologic-response-and-hospitalization-rate-of-patients-receiving-cabazitaxel-in-the-fourth-line-and-beyond-in-castration-resistant-prostate-cancer-analysis-of-a-retrospective-cohort-and-a-structured-literature-review
#8
Jost von Hardenberg, Maike Schwartz, Thorsten Werner, Stefan Fuxius, Arne Strauss, Thomas Stefan Worst, Philipp Nuhn, Christian Bolenz, Elmar Heinrich
BACKGROUND: Limited data are available for the use of agents in metastatic castration-resistant prostate cancer (mCRPC) beyond the third-line. We provide data during treatment with cabazitaxel (CAB), helping to improve the informed-consent process. PATIENTS AND METHODS: We retrospectively reviewed patients treated with fourth-line or beyond CAB for mCRPC after failure of previous therapies with docetaxel, abiraterone acetate, enzalutamide and/or radium-223. The progression-free survival (PFS) and the overall survival (OS) were estimated using the Kaplan-Meier method and compared to published data based on a structured literature review...
July 13, 2017: Urologia Internationalis
https://www.readbyqxmd.com/read/28698198/abcb1-mediates-cabazitaxel-docetaxel-cross-resistance-in-advanced-prostate-cancer
#9
Alan P Lombard, Chengfei Liu, Cameron M Armstrong, Vito Cucchiara, Xinwei Gu, Wei Lou, Christopher P Evans, Allen C Gao
in research have added several new therapies for castration-resistant prostate cancer (CRPC), greatly augmenting our ability to treat patients. However, CRPC remains an incurable disease due to the development of therapeutic resistance and the existence of cross-resistance between available therapies. Understanding the interplay between different treatments will lead to improved sequencing and the creation of combinations which overcome resistance and prolong survival. Whether there exists cross-resistance between docetaxel and the next-generation taxane cabazitaxel is poorly understood...
July 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28691182/hsp70-inhibitors-suppress-androgen-receptor-expression-in-lncap95-prostate-cancer-cells
#10
Kazuaki Kita, Masayuki Shiota, Masako Tanaka, Asuka Otsuka, Masaki Matsumoto, Minoru Kato, Satoshi Tamada, Hiroshi Iwao, Katsuyuki Miura, Tatsuya Nakatani, Shuhei Tomita
Androgen deprivation therapy (ADT) is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to ADT, which is termed castration-resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR-V7), one of the causes of CRPC, is correlated with the resistance to a new-generation AR antagonist (enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is known to decrease the levels of full-length AR (AR-FL), but little is known about its effects against CRPC cells expressing AR-V7...
July 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28682871/post-hoc-analyses-of-east-asian-patients-from-the-randomized-placebo-controlled-prevail-trial-of-enzalutamide-in-patients-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#11
RANDOMIZED CONTROLLED TRIAL
Choung Soo Kim, Young Deuk Choi, Sang Eun Lee, Hyun Moo Lee, Takeshi Ueda, Junji Yonese, Takashi Fukagai, Edmund Chiong, Weber Lau, Sarang Abhyankar, Ad Theeuwes, Bertrand Tombal, Tomasz M Beer, Go Kimura
BACKGROUND: Enzalutamide is an androgen receptor (AR) inhibitor that acts on different steps in the AR signaling pathway. In PREVAIL, an international, phase III, double-blind, placebo-controlled trial, enzalutamide significantly reduced the risk of radiographic progression by 81% (hazard ratio [HR], 0.19; P < .0001) and reduced the risk of death by 29% (HR, 0.71; P < .0001) compared with placebo in chemotherapy-naïve men with metastatic castration-resistant prostate cancer...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28668854/pca3-silencing-sensitizes-prostate-cancer-cells-to-enzalutamide-mediated-androgen-receptor-blockade
#12
Emre Özgür, Ayca Iribas Celik, Emin Darendeliler, Ugur Gezer
BACKGROUND/AIM: Prostate cancer (PCa) is an androgen-dependent disease. Novel anti-androgens (i.e. enzalutamide) have recently been developed for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Evidence is accumulating that prostate cancer antigen 3 (PCA3) is involved in androgen receptor (AR) signaling. Here, in combination with enzalutamide-mediated AR blockade, we investigated the effect of PCA3 targeting on the viability of PCa cells. MATERIALS AND METHODS: In hormone-sensitive LNCaP cells, AR-overexpressing LNCaP-AR(+) cells and VCaP cells (representing CRPC), PCA3 was silenced using siRNA oligonucleotides...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28655021/the-diagnosis-and-treatment-of-prostate-cancer-a-review
#13
REVIEW
Mark S Litwin, Hung-Jui Tan
Importance: Prostate cancer is the most common cancer diagnosis made in men with more than 160 000 new cases each year in the United States. Although it often has an indolent course, prostate cancer remains the third-leading cause of cancer death in men. Observations: When prostate cancer is suspected, tissue biopsy remains the standard of care for diagnosis. However, the identification and characterization of the disease have become increasingly precise through improved risk stratification and advances in magnetic resonance and functional imaging, as well as from the emergence of biomarkers...
June 27, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28649702/dose-considerations-for-anti-cancer-drugs-in-metastatic-prostate-cancer
#14
REVIEW
Megan Crumbaker, Howard Gurney
Despite a growing number of treatment options, metastatic castrate resistant prostate cancer remains almost universally fatal. Dose individualization ensures patients receive the maximal benefit from each line of treatment potentially leading to improved outcomes, a reduction in quality of life impairment and minimization of premature cessation for avoidable toxicity. Herein, we review drug-specific issues that may be associated with unexpected or unrecognized variations in drug systemic exposure despite the use of protocol doses...
June 26, 2017: Prostate
https://www.readbyqxmd.com/read/28645287/health-related-quality-of-life-effects-of-enzalutamide-in-patients-with-metastatic-castration-resistant-prostate-cancer-an-in-depth-post-hoc-analysis-of-eq-5d-data-from-the-prevail-trial
#15
Nancy Devlin, Michael Herdman, Marco Pavesi, De Phung, Shevani Naidoo, Tomasz M Beer, Bertrand Tombal, Yohann Loriot, Cristina Ivanescu, Teresa Parli, Mark Balk, Stefan Holmstrom
BACKGROUND: The effect of enzalutamide on health-related quality of life (HRQoL) in the PREVAIL trial in chemotherapy-naïve men with metastatic castration-resistant prostate cancer was analyzed using the generic EQ-5D instrument. METHODS: Patients received oral enzalutamide 160 mg/day (n = 872) or placebo (n = 845). EQ-5D index and EQ-5D visual analogue scale (EQ-5D VAS) scores were evaluated at baseline, week 13, and every 12 weeks until week 61 due to sample size reduction thereafter...
June 23, 2017: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/28644302/the-role-of-bone-targeted-therapies-for-prostate-cancer-in-2017
#16
Samer L Traboulsi, Fred Saad
PURPOSE OF REVIEW: Bone-targeted agents (BTAs), such as zoledronic acid and denosumab, delay the occurrence of skeletal-related events (SREs) in metastatic prostate cancer (PCa) patients. Recently, several agents, such as abiraterone acetate, enzalutamide and radium-223, were approved for the treatment of metastatic castration-resistant PCa (mCRPC). These agents resulted in improved overall survival (OS), pain control and had positive effects on bone health. Combining BTAs to the newly approved agents demonstrates additional benefits that warrant a review of available evidence looking at appropriate combination therapies and timing of BTAs for optimizing the management of advanced and metastatic PCa...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28642838/adaptive-pathways-and-emerging-strategies-overcoming-treatment-resistance-in-castration-resistant-prostate-cancer
#17
Cameron M Armstrong, Allen C Gao
The therapies available for prostate cancer patients whom progress from hormone-sensitive to castration resistant prostate cancer include both systemic drugs, including docetaxel and cabazitaxel, and drugs that inhibit androgen signaling such as enzalutamide and abiraterone. Unfortunately, it is estimated that up to 30% of patients have primary resistance to these treatments and over time even those who initially respond to therapy will eventually develop resistance and their disease will continue to progress regardless of the presence of the drug...
October 2016: Asian Journal of Urology
https://www.readbyqxmd.com/read/28638477/triptolide-inhibits-the-ar-signaling-pathway-to-suppress-the-proliferation-of-enzalutamide-resistant-prostate-cancer-cells
#18
Yangyang Han, Weiwei Huang, Jiakuan Liu, Dandan Liu, Yangyan Cui, Ruimin Huang, Jun Yan, Ming Lei
Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown...
2017: Theranostics
https://www.readbyqxmd.com/read/28636139/review-of-hplc-and-lc-ms-ms-assays-for-the-determination-of-various-non-steroidal-anti-androgens-nsaa-used-in-the-treatment-of-prostate-cancer
#19
REVIEW
P S Suresh, Nuggehally R Srinivas, Ramesh Mullangi
Prostate cancer is the most common cancer and one of the leading causes for cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first generation non-steroidal anti-androgens (NSAA) namely flutamide, nilutamide, bicalutamide and topilutamide. Most of the prostate cancer patients who are initially responsive develop a most aggressive form of disease called castration-resistant prostate cancer (CRPC). Second generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat CRPC...
June 21, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28628393/early-national-dissemination-of-abiraterone-and-enzalutamide-for-advanced-prostate-cancer-in-medicare-part-d
#20
Megan E V Caram, Tudor Borza, Hye-Sung Min, Jennifer J Griggs, David C Miller, Brent K Hollenbeck, Bhramar Mukherjee, Ted A Skolarus
INTRODUCTION: Abiraterone and enzalutamide were approved by the Food and Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer (mCRPC). Most men with mCRPC are > 65 years of age and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D data. METHODS: We evaluated the number of prescriptions for abiraterone and enzalutamide by provider specialty and hospital referral region (HRR) using Medicare Part D and Dartmouth Atlas data...
June 19, 2017: Journal of Oncology Practice
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