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Enzalutamide resistance

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https://www.readbyqxmd.com/read/28444169/androgen-receptor-regulation-of-local-growth-hormone-in-prostate-cancer-cells
#1
M V Recouvreux, B Wu, A C Gao, S Zonis, V Chesnokova, N Bhowmick, L W Chung, S Melmed
Prostate cancer (PCa) growth is mainly driven by androgen receptor (AR), and tumors that initially respond to androgen deprivation therapy (ADT) or AR inhibition usually relapse into a more aggressive, castration resistant stage (CRPC). Circulating growth hormone (GH) has a permissive role in PCa development in animal models and in human PCa xenograft growth. As GH and GH receptor (GHR) are both expressed in PCa cells, we assessed whether prostatic GH production is linked to AR activity and whether GH contributes to the castration resistant phenotype...
April 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28441112/second-line-hormonal-therapy-for-men-with-chemotherapy-na%C3%A3-ve-castration-resistant-prostate-cancer-american-society-of-clinical-oncology-provisional-clinical-opinion
#2
Katherine S Virgo, Ethan Basch, D Andrew Loblaw, Tom Oliver, R Bryan Rumble, Michael A Carducci, Luke Nordquist, Mary-Ellen Taplin, Eric Winquist, Eric A Singer
Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies...
April 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#3
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426107/controversies-and-consensus-in-the-innovation-access-for-cancer-therapy-in-the-european-countries-on-the-subject-of-metastatic-prostate-cancer
#4
S Oudard, F Courbon
Innovative cancer therapies and advances in drug development have created new hopes for patients and health providers. The purpose of this article was to evaluate the discrepancies in the assessment of the magnitude of benefit of four new drugs (abiraterone acetate, enzalutamide, cabazitaxel, radium-223 dichloride) for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The comparison was done among three European countries (UK, Germany and France) and Canada, according to the statement of each country and to the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28414609/association-between-androgen-receptor-splice-variants-and-prostate-cancer-resistance-to-abiraterone-and-enzalutamide
#5
Glenn J Bubley, Steven P Balk
No abstract text is available yet for this article.
April 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28413979/drug-resistance-of-enzalutamide-in-crpc
#6
Xuedong Chen, Jieyang Lu, Liqun Xia, Gonghui Li
Enzalutamide (MDV3100, XTANDI ) is a second generation androgen receptor inhibitor that is designed for the treatment of castration-resistant prostate cancer (CRPC) and has prolonged survival time. Although Enzalutamide was also associated with such significant benefits, The majority of treated patients, innate or acquired resistance invariably arises, but the mechanisms of mdv3100 resistance have not yet been clearly clarified. Nevertheless, because the better knowledge of the genetic landscape of MDV3100 is under way, resistance to MDV3100 could be basically divided in two distinct pathways, either dependent or independent of the androgen receptor activity...
April 17, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28395931/impact-of-abiraterone-acetate-and-enzalutamide-on-symptom-burden-of-patients-with-chemotherapy-naive-metastatic-castration-resistant-prostate-cancer
#7
S Salem, M Komisarenko, N Timilshina, L Martin, R Grewal, S Alibhai, A Finelli
AIMS: Treatments and disease burden of metastatic castration-resistant prostate cancer (mCRPC) considerably affect a patient's quality of life. However, patient-reported symptom burden data are still largely insufficient. This study sought to compare the self-reported symptom burden of men with chemotherapy-naive (CN) mCRPC treated with abiraterone acetate (AA) or enzalutamide (EZ) in routine clinical practice. MATERIALS AND METHODS: Between 2011 and 2015, 189 CN-mCRPC patients who had received AA (n = 76) or EZ (n = 113) at the Princess Margaret Cancer Centre were included...
April 8, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28390646/first-line-management-of-metastatic-castrate-resistant-prostate-cancer-patients-audit-of-real-life-practices
#8
Anthony Turpin, David Pasquier, Christophe Massard, Jean-François Berdah, Stéphane Culine, Nicolas Penel
BACKGROUND: No reliable guidelines are available for choosing the best option between docetaxel and new hormonal therapies (NHTs) (i.e., abiraterone and enzalutamide) in first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. We performed an audit of real-life practices. METHODS: We built an online questionnaire and distributed it with the help of French oncology networks. This questionnaire was sent to 481 physicians who treat patients with mCRPC...
April 5, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28384066/clinical-significance-of-androgen-receptor-splice-variant-7-mrna-detection-in-circulating-tumor-cells-of-men-with-metastatic-castration-resistant-prostate-cancer-treated-with-first-and-second-line-abiraterone-and-enzalutamide
#9
Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Hao Wang, Yan Chen, Yezi Zhu, John L Silberstein, Maritza N Taylor, Benjamin L Maughan, Samuel R Denmeade, Kenneth J Pienta, Channing J Paller, Michael A Carducci, Mario A Eisenberger, Jun Luo
Purpose We reported previously that the detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumor cells (CTCs) correlated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration-resistant prostate cancer (CRPC). Here, we expanded our cohort size to better characterize the prognostic significance of AR-V7 in this setting. Methods We prospectively enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigated the prognostic value of CTC detection (+ v -) and AR-V7 detection (+ v -) using a CTC-based AR-V7 mRNA assay...
April 6, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28373004/natural-killer-cells-suppress-enzalutamide-resistance-and-cell-invasion-in-the-castration-resistant-prostate-cancer-via-targeting-the-androgen-receptor-splicing-variant-7-arv7
#10
Shin-Jen Lin, Fu-Ju Chou, Lei Li, Chang-Yi Lin, Shuyuan Yeh, Chawnshang Chang
Despite the success of androgen-deprivation therapy (ADT) with the newly developed anti-androgen enzalutamide (Enz, also known as MDV3100) to suppress castration resistant prostate cancer (CRPC) in extending patient survival by an extra 4.8 months, eventually patients die with the development of Enz resistance that may involve the induction of the androgen receptor (AR) splicing variant ARv7. Here we identify an unrecognized role of Natural Killer (NK) cells in the prostate tumor microenvironment that can be better recruited to the CRPC cells to suppress ARv7 expression resulting in suppressing the Enz resistant CRPC cell growth and invasion...
March 31, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28368512/androgen-receptor-rearrangement-and-splicing-variants-in-resistance-to-endocrine-therapies-in-prostate-cancer
#11
Yeung Ho, Scott M Dehm
The past few years have witnessed a significant improvement in the survival of patients with castration-resistant prostate cancer (CRPC) due to the development of second generation androgen deprivation therapies (ADT) such as abiraterone and second generation antagonists such as enzalutamide. However, CRPC patients rapidly develop resistance to these drugs, in many cases due to re-activation of the therapeutic target, the androgen receptor (AR) transcription factor. Several mechanisms responsible for AR transcriptional re-activation have been demonstrated, including mutation, amplification, or rearrangement of the AR gene, transcriptional compensation by alternative steroid receptors, and mutation or copy number alteration of genes encoding AR co-regulators...
March 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28367230/efficacy-of-cabazitaxel-treatment-in-metastatic-castration-resistant-prostate-cancer-in-second-and-later-lines-an-experience-from-two-german-centers
#12
Stefanie Zschäbitz, Sonia Vallet, Boris Hadaschik, Daniel Debatin, Stefan Fuxius, Andreas Karcher, Sascha Pahernik, Cathleen Spath, Stefan Duensing, Dirk Jäger, Markus Hohenfellner, Carsten Grüllich
Purpose: Several new treatment options for patients with metastatic castration resistant prostate cancer (mCRPC) have been approved within the last years - among them cabazitaxel (CAB), abiraterone acetate, enzalutamide, and radium-223. The aim of this study was to assess factors predictive for efficacy of CAB. Methods: We analyzed all patients with mCRPC treated with CAB at our institutions between 2011 and 2016. Data were retrieved retrospectively from the electronical patient chart. Results: 69 patients received CAB (26...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28365160/bipolar-androgen-therapy-a-paradoxical-approach-for-the-treatment-of-castration-resistant-prostate-cancer
#13
EDITORIAL
Michael T Schweizer, Emmanuel S Antonarakis, Samuel R Denmeade
Bipolar androgen therapy (BAT) is a paradoxical treatment for castrate-resistant prostate cancer whereby testosterone levels are rapidly alternated between supraphysiologic and near-castrate concentrations. Initial studies demonstrated that BAT is safe and produces clinical responses. A trial comparing enzalutamide against BAT is ongoing.
March 29, 2017: European Urology
https://www.readbyqxmd.com/read/28361045/phase-i-clinical-trial-of-sipuleucel-t-combined-with-escalating-doses-of-ipilimumab-in-progressive-metastatic-castrate-resistant-prostate-cancer
#14
Mark Scholz, Sabrina Yep, Micah Chancey, Colleen Kelly, Ken Chau, Jeffrey Turner, Richard Lam, Charles G Drake
BACKGROUND: Sipuleucel-T (SIP-T), which functions by stimulating cancer-specific dendritic cells, prolongs survival in men with prostate cancer. Ipilimumab (IPI) achieved a borderline survival advantage in a large randomized trial. SIP-T and IPI are potentially synergistic. PATIENTS AND METHODS: Nine men with progressive metastatic castrate-resistant prostate cancer (mCRPC) were treated prospectively with SIP-T followed immediately by IPI with one of the following doses of IPI: 1 mg/kg at 1 week after SIP-T; 1 mg/kg at 1 and 4 weeks after SIP-T; or 1 mg/kg at 1, 4, and 7 weeks after SIP-T...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28360139/a-pyrrole-imidazole-polyamide-is-active-against-enzalutamide-resistant-prostate-cancer
#15
Alexis A Kurmis, Fei Yang, Timothy R Welch, Nicholas G Nickols, Peter B Dervan
The LREX' prostate cancer model is resistant to the antiandrogen enzalutamide via activation of an alternative nuclear hormone receptor (NHR), glucocorticoid receptor (GR), which has similar DNA binding specificity to the androgen receptor (AR). Small molecules that target DNA to interfere with protein-DNA interactions may retain activity against enzalutamide-resistant prostate cancers where ligand binding domain antagonists are ineffective. We reported previously that a pyrrole-imidazole (Py-Im) polyamide designed to bind the consensus androgen response element half-site has antitumor activity against hormone-sensitive prostate cancer...
March 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28353036/resistance-to-hormonal-therapy-in-prostate-cancer
#16
Alfredo Berruti, Alberto Dalla Volta
Several therapeutic strategies are actually available in the management of prostate cancer: Targeting the androgen receptor (AR) is the goal both for initial androgen deprivation therapy (ADT) and second-generation androgen ablative agents (abiraterone and enzalutamide). Chemotherapy with taxanes, administered upon progression or as first line approach in association with ADT, is another therapeutic option. Unfortunately, none of these therapies is curative and patients are destined to develop a resistant phenotype...
March 29, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28345444/budgetary-impact-of-cabazitaxel-use-after-docetaxel-treatment-for-metastatic-castration-resistant-prostate-cancer
#17
Kyle Flannery, Ed Drea, Louis Hudspeth, Shelby Corman, Xin Gao, Mei Xue, Raymond Miao
BACKGROUND: With the approval of several new treatments for metastatic castration-resistant prostate cancer (mCRPC), budgetary impact is a concern for health plan decision makers. Budget impact models (BIMs) are becoming a requirement in many countries as part of formulary approval or reimbursement decisions. Cabazitaxel is a second-generation taxane developed to overcome resistance to docetaxel and is approved for the treatment of patients with mCRPC previously treated with a docetaxel-containing regimen...
April 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28344102/effect-of-visceral-disease-site-on-outcomes-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-enzalutamide-in-the-prevail-trial
#18
Joshi J Alumkal, Simon Chowdhury, Yohann Loriot, Cora N Sternberg, Johann S de Bono, Bertrand Tombal, Joan Carles, Thomas W Flaig, Tanya B Dorff, De Phung, David Forer, Sarah B Noonberg, Hank Mansbach, Tomasz M Beer, Celestia S Higano
BACKGROUND: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy...
March 3, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28323658/changing-face-of-metastatic-prostate-cancer-the-law-of-diminishing-returns-holds-true
#19
Ulka N Vaishampayan
PURPOSE OF REVIEW: Prostate cancer presents with a multitude of faces. It ranges from localized cancers staying quiescent for many years during active surveillance to the raging diffuse liver metastases causing terminal disease. The incidence of metastatic disease is increasing. This review will highlight some of the recent developments as well as ongoing challenges of managing advanced prostate cancer. RECENT FINDINGS: Significant strides are being made in managing metastatic prostate cancer...
March 18, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28323036/targeting-androgen-receptor-versus-targeting-androgens-to-suppress-castration-resistant-prostate-cancer
#20
Changcheng Guo, Shuyuan Yeh, Yuanjie Niu, Gonghui Li, Junhua Zheng, Lei Li, Chawnshang Chang
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941...
March 18, 2017: Cancer Letters
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