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https://www.readbyqxmd.com/read/28609657/ack1-tnk2-regulates-histone-h4-tyr88-phosphorylation-and-ar-gene-expression-in-castration-resistant-prostate-cancer
#1
Kiran Mahajan, Pavani Malla, Harshani R Lawrence, Zhihua Chen, Chandan Kumar-Sinha, Rohit Malik, Sudhanshu Shukla, Jongphil Kim, Domenico Coppola, Nicholas J Lawrence, Nupam P Mahajan
The androgen receptor (AR) is critical for the progression of prostate cancer to a castration-resistant (CRPC) state. AR antagonists are ineffective due to their inability to repress the expression of AR or its splice variant, AR-V7. Here, we report that the tyrosine kinase ACK1 (TNK2) phosphorylates histone H4 at tyrosine 88 upstream of the AR transcription start site. The WDR5/MLL2 complex reads the H4-Y88-phosphorylation marks and deposits the transcriptionally activating H3K4-trimethyl marks promoting AR transcription...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28600675/a-novel-capillary-nano-immunoassay-for-assessing-androgen-receptor-splice-variant-7-in-plasma-correlation-with-cd133-antigen-expression-in-circulating-tumor-cells-a-pilot-study-in-prostate-cancer-patients
#2
J L García, R Lozano, I Misiewicz-Krzeminska, J Fernández-Mateos, P Krzeminski, S Alfonso, R A Marcos, R García, F Gómez-Veiga, Á Virseda, M Herrero, D Olmos, J J Cruz-Hernández
PURPOSE: Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. METHODS: Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform...
June 9, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28598696/pathology-and-molecular-updates-in-tumors-of-the-prostate-towards-a-personalized-approach
#3
Silvia Gasparrini, Alessia Cimadamore, Roberta Mazzucchelli, Marina Scarpelli, Francesco Massari, Maria Rosaria Raspollini, Andrea B Galosi, Antonio Lopez-Beltran, Liang Cheng, Rodolfo Montironi
Treatment planning in patients with prostate neoplasms and prostate cancer (PCa) is generally based on the clinical and pathological molecular markers obtained from prostate needle biopsy and/or radical prostatectomy specimens. Area covered: Pathology of prostate neoplasms is evolving rapidly. Emerging trends include new additions to the 2016 World Health Organization (WHO) tumor classification as well as expanded diagnostic utility of biomarkers and molecular testing in tissue specimens, liquid biopsies and urinary samples, with the following purposes: diagnosis, prognosis and prediction...
June 15, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28590268/ar-v7-liquid-biopsy-for-treatment-stratification-in-prostate-cancer-how-close-are-we
#4
Claire Fletcher
PURPOSE OF REVIEW: Recent clinical introduction of the novel antiandrogen, Enzalutamide (Enza), CYP17 inhibitor, Abiraterone (Abi), and the second-generation chemotherapeutic, Cabazitaxel, has increased survival of patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). However, de novo and acquired resistance rates are high. A liquid biopsy that can rapidly, sensitively and robustly identify which patients will respond to treatment in a minimally invasive manner is urgently required to permit switch to a potentially more efficacious drug regimen, thus increasing survival whilst avoiding debilitating side effects associated with unnecessary treatment...
June 5, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28561752/melatonin-inhibits-androgen-receptor-splice-variant-7-ar-v7-induced-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-activation-and-nf-%C3%AE%C2%BAb-activator-induced-ar-v7-expression-in-prostate-cancer-cells-potential-implications-for-the-use-of-melatonin-in-castration-resistant-prostate
#5
Vincent Wing Sun Liu, Wing Lung Yau, Chun Wai Tam, Kwok-Ming Yao, Stephen Yuen Wing Shiu
A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin (IL)-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis...
May 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28559013/establishment-and-genomic-characterization-of-primary-salivary-duct-carcinoma-cell-line
#6
Jie Li, Yohitsugu Mitani, Pulivarthi H Rao, Laszlo Perlaky, Bin Liu, Randal S Weber, Adel K El-Naggar
OBJECTIVES: To develop and characterize in vitro salivary duct carcinoma as a surrogate for functional studies. MATERIALS AND METHODS: Cells were dispersed from tumor tissue fragments under sterile conditions in RPMI media. Disassociated cells were cultivated, immortalized with hTERT and propagated for more than 100 passages. Morphologic, linage, cytogenetic and genomic analyses were performed on different passages of cell line and primary tumor. Soft agar growth was performed...
June 2017: Oral Oncology
https://www.readbyqxmd.com/read/28528814/preclinical-study-using-malat1-small-interfering-rna-or-androgen-receptor-splicing-variant-7-degradation-enhancer-asc-j9-%C3%A2-to-suppress-enzalutamide-resistant-prostate-cancer-progression
#7
Ronghao Wang, Yin Sun, Lei Li, Yuanjie Niu, Wanying Lin, Changyi Lin, Emmanuel S Antonarakis, Jun Luo, Shuyuan Yeh, Chawnshang Chang
BACKGROUND: While androgen-deprivation-therapy with the recently developed antiandrogen enzalutamide (Enz) shows promising therapeutic benefits in men with metastatic castration-resistant prostate cancer (PCa), many patients develop resistance to Enz, which may involve the induction of the androgen receptor (AR) splicing variant 7 (AR-v7). OBJECTIVE: Our aim is to identify the mechanisms responsible for AR-v7 production and to develop novel preclinical approaches to suppress the Enz-resistant (EnzR) PCa...
May 18, 2017: European Urology
https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#8
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
June 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28500234/niclosamide-and-bicalutamide-combination-treatment-overcomes-enzalutamide-and-bicalutamide-resistant-prostate-cancer
#9
Chengfei Liu, Cameron M Armstrong, Wei Lou, Alan P Lombard, Vito Cucchiara, Xinwei Gu, Joy C Yang, Nagalakshmi Nadiminty, Chong-Xian Pan, Christopher P Evans, Allen C Gao
Activation of the androgen receptor (AR) and its splice variants is linked to advanced prostate cancer and drives resistance to antiandrogens. The roles of AR and AR variants in the development of resistance to androgen deprivation therapy (ADT) and bicalutamide treatment, however, are still incompletely understood. To determine whether AR variants play a role in bicalutamide resistance, we developed bicalutamide resistant LNCaP cells (LNCaP-BicR) and found that these resistant cells express significantly increased levels of AR variants, particularly AR-V7, both at the mRNA and protein levels...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28498452/calpain-and-ar-v7-two-potential-therapeutic-targets-to-overcome-acquired-docetaxel-resistance-in-castration-resistant-prostate-cancer-cells
#10
Lei Liu, Ning Lou, Xiang Li, Guanghua Xu, Hailong Ruan, Wen Xiao, Bin Qiu, Lin Bao, Changfei Yuan, Xinmian Huang, Keshan Wang, Qi Cao, Ke Chen, Hongmei Yang, Xiaoping Zhang
Docetaxel-based chemotherapy has been widely used as the first-line treatment for castration-resistant prostate cancer (CRPC) patients. However, the mechanisms of docetaxel-resistance remain unclear. In the present study with the establishment of 2 in vitro models of docetaxel-resistant CRPC cell sublines, we firstly reported that activation of calpain may play a promotional role in the resistance of docetaxel in prostate cancer, meanwhile using the calpain inhibitor combined with docetaxel improved the efficiency of docetaxel in docetaxel-resistant cell sublines...
May 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28498319/ctc-mrna-ar-v7-analysis-from-blood-samples-impact-of-blood-collection-tube-and-storage-time
#11
Alison W S Luk, Yafeng Ma, Pei N Ding, Francis P Young, Wei Chua, Bavanthi Balakrishnar, Daniel T Dransfield, Paul de Souza, Therese M Becker
Circulating tumour cells (CTCs) are an emerging resource for monitoring cancer biomarkers. New technologies for CTC isolation and biomarker detection are increasingly sensitive, however, the ideal blood storage conditions to preserve CTC-specific mRNA biomarkers remains undetermined. Here we tested the preservation of tumour cells and CTC-mRNA over time in common anticoagulant ethylene-diamine-tetra-acetic acid (EDTA) and acid citrate dextrose solution B (Citrate) blood tubes compared to preservative-containing blood tubes...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28473535/androgen-receptor-variant-ar-v9-is-co-expressed-with-ar-v7-in-prostate-cancer-metastases-and-predicts-abiraterone-resistance
#12
Manish Kohli, Yeung Ho, David W Hillman, Jamie L Van Etten, Christine Henzler, Rendong Yang, Jame M Sperger, Yingming Li, Elizabeth Tseng, Ting Hon, Tyson Clark, Winston Tan, Rachel E Carlson, Liguo Wang, Hugues Sicotte, Ho Thai, Rafael Jimenez, Haojie Huang, Peter T Vedell, Bruce W Eckloff, J Fernando Quevedo, Henry C Pitot, Brian Costello, Jin Jen, Eric D Wieben, Kevin A T Silverstein, Joshua M Lang, Liewei Wang, Scott M Dehm
Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies.  Accordingly, efforts are underway to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC).  The purpose of this study was to understand whether other AR variants may be co-expressed with AR-V7 and promote resistance to AR-targeted therapies.<br /><br /> Experimental Design:  We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models...
May 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28397338/glycogen-synthase-kinase-3-inhibitors-suppress-the-ar-v7-mediated-transcription-and-selectively-inhibit-cell-growth-in-ar-v7-positive-prostate-cancer-cells
#13
Daisuke Nakata, Ryokichi Koyama, Kazuhide Nakayama, Satoshi Kitazawa, Tatsuya Watanabe, Takahito Hara
BACKGROUND: Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. METHODS: High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system...
June 2017: Prostate
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
#14
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/28365708/resistenzentwicklung-und-pr%C3%A3-diktive-marker-beim-metastasierten-prostatakarzinom
#15
Christof Bernemann, Martin Bögemann, Julie Steinestel, Andreas Jan Schrader
Anders als bei vielen anderen Krebserkrankungen gab es beim Prostatakarzinom lange Zeit keinen Ansatz für eine individualisierte Therapie. Seit der Zulassung von mehreren modernen Wirkstoffen für die Therapie des fortgeschrittenen Stadiums ändert sich dies allmählich. Zunächst galt die Androgenrezeptor-Splice-Variante AR-V7 als vielversprechender Biomarker für die Therapiesteuerung, woran sich zunehmend Zweifel mehren. Inzwischen gibt es jedoch eine Reihe von weiteren neuen, noch nicht zugelassenen und nicht (nur) auf den Androgenrezeptor fokussierenden Therapieansätzen, die auch beim fortgeschrittenen Prostatakarzinom eine personalisierte Medizin wahrscheinlicher machen...
2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28277880/genomic-tests-to-guide-prostate-cancer-management-following-diagnosis
#16
Michele Colicchia, Alessandro Morlacco, John C Cheville, R Jeffrey Karnes
Prostate cancer (PCa) is a common cancer in men, but variable clinical behaviors make its management challenging. Risk stratification is a key issue in disease management. Patient-tailored strategies are strongly advocated to reduce unnecessary treatment while maximizing the oncological outcomes of patient who need active treatment in the primary, adjuvant or salvage setting. Recently, tissue-based biomarkers or genomic tests have become available to improve the clinical decision-making. Areas covered: In this review, the authors present recent evidence about these tissue-based biomarkers, discussing the application of each of them in the clinical setting, focusing on the tests aimed to provide a better risk stratification and to guide decision-making after the diagnosis of PCa (i...
March 13, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28239558/role-of-androgen-receptor-splice-variants-in-prostate-cancer-metastasis
#17
Jin Xu, Yun Qiu
Prostate cancer (PCa) is one of the most lethal cancers in western countries. Androgen receptor (AR) signaling pathway plays a key role in PCa progression. Despite the initial effectiveness of androgen deprivation therapy (ADT) for treatment of patients with advanced PCa, most of them will develop resistance to ADT and progress to metastatic castration resistant prostate cancer (mCRPC). Constitutively transcriptional activated AR splice variants (AR-Vs) have emerged as critical players in the development and progression of mCRPC...
October 2016: Asian Journal of Urology
https://www.readbyqxmd.com/read/28209757/cdk4-6-therapeutic-intervention-and-viable-alternative-to-taxanes-in-crpc
#18
James P Stice, Suzanne E Wardell, John D Norris, Alexander P Yllanes, Holly M Alley, Victoria O Haney, Hannah S White, Rachid Safi, Peter S Winter, Kimberly J Cocce, Rigel J Kishton, Scott A Lawrence, Jay C Strum, Donald P McDonnell
Resistance to second-generation androgen receptor (AR) antagonists and CYP17 inhibitors in patients with castration-resistant prostate cancer (CRPC) develops rapidly through reactivation of the androgen signaling axis and has been attributed to AR overexpression, production of constitutively active AR splice variants, or the selection for AR mutants with altered ligand-binding specificity. It has been established that androgens induce cell-cycle progression, in part, through upregulation of cyclin D1 (CCND1) expression and subsequent activation of cyclin-dependent kinases 4 and 6 (CDK4/6)...
June 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28205582/aurora-a-regulates-expression-of-ar-v7-in-models-of-castrate-resistant-prostate-cancer
#19
Dominic Jones, Martin Noble, Steve R Wedge, Craig N Robson, Luke Gaughan
Androgen receptor variants (AR-Vs) provide a mechanism of therapy evasion in castrate-resistant prostate cancer (CRPC), yet mechanisms of regulation remain largely unknown. Here we investigate the role of Aurora A kinase on AR-Vs in models of CRPC and show depletion of Aurora A reduces AR-V target gene expression. Importantly, knockdown of Aurora A reconfigures splicing of AR pre-mRNA to discriminately down-regulate synthesis of AR-V transcripts, including AR-V7, without effecting full-length AR mRNA; and as a consequence, AR-V-driven proliferation and survival of CRPC cells is markedly reduced...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28144969/high-levels-of-the-ar-v7-splice-variant-and-co-amplification-of-the-golgi-protein-coding-yipf6-in-ar-amplified-prostate-cancer-bone-metastases
#20
Erik Djusberg, Emma Jernberg, Elin Thysell, Irina Golovleva, Pia Lundberg, Sead Crnalic, Anders Widmark, Anders Bergh, Maria Brattsand, Pernilla Wikström
BACKGROUND: The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistant prostate cancer (CRPC), such as expression of constitutively active AR variants and steroid-converting enzymes has been poorly examined. Specific aim was to examine AR amplification in PC bone metastases and to explore molecular and functional consequences of this, with the long-term goal of identifying novel molecular targets for treatment. METHODS: Gene amplification was assessed by fluorescence in situ hybridization in cryo-sections of clinical PC bone metastases (n = 40) and by PCR-based copy number variation analysis...
February 1, 2017: Prostate
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