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https://www.readbyqxmd.com/read/28818355/ar-v7-in-peripheral-whole-blood-of-patients-with-castration-resistant-prostate-cancer-association-with-treatment-specific-outcome-under-abiraterone-and-enzalutamide
#1
Anna Katharina Seitz, Silvia Thoene, Andreas Bietenbeck, Roman Nawroth, Robert Tauber, Mark Thalgott, Sebastian Schmid, Ramona Secci, Margitta Retz, Jürgen E Gschwend, Jürgen Ruland, Christof Winter, Matthias M Heck
BACKGROUND: It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide. OBJECTIVE: To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients...
August 14, 2017: European Urology
https://www.readbyqxmd.com/read/28811363/targeting-ar-variant-coactivator-interactions-to-exploit-prostate-cancer-vulnerabilities
#2
Fiorella Magani, Stephanie O Peacock, Meghan A Rice, Maria J Martinez, Ann M Greene, Pablo S Magani, Rolando Lyles, Jonathan R Weitz, Kerry L Burnstein
Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced PC. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28811331/targeting-a-single-alternative-polyadenylation-site-coordinately-blocks-expression-of-androgen-receptor-mrna-splice-variants-in-prostate%C3%A2-cancer
#3
Jamie L Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel M Johnson, Olivia Ondigi, Daniel F Voytas, Christine Henzler, Scott M Dehm
Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28808043/allosteric-alterations-in-the-androgen-receptor-and-activity-in-prostate-cancer
#4
REVIEW
Takuma Uo, Stephen R Plymate, Cynthia C Sprenger
Organisms have evolved to generate biological complexity in their proteome and transcriptome from a limited number of genes. This concept holds true for the androgen receptor, which displays a diversity of inclusion/exclusion events in its structural motifs as a mechanism of resistance to the most forefront anti-androgen therapies. More than 20 androgen receptor variants that lack various portions of ligand-binding domain have been identified in human prostate cancer (PCa) samples. Most of the variants are inactive on their own, with a few exceptions displaying constitutive activity...
September 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28783103/significance-of-micrornas-in-androgen-signaling-and-prostate-cancer-progression
#5
REVIEW
Ken-Ichi Takayama, Aya Misawa, Satoshi Inoue
The androgen receptor (AR) plays important roles in prostate cancer development and prostate tumor growth. After binding to androgens, AR functions as a nuclear receptor and translocates to the nucleus to bind to specific AR-binding sites (ARBSs). AR regulates epigenetic factor recruitments to activate its downstream signaling. Although androgen deprivation therapy (ADT) is initially useful for prostate cancer patients, most patients eventually show resistance with hormone-refractory prostate cancers (HRPCs) or castration-resistant prostate cancers (CRPCs)...
August 7, 2017: Cancers
https://www.readbyqxmd.com/read/28775145/bypassing-drug-resistance-mechanisms-of-prostate-cancer-with-small-molecules-that-target-androgen-receptor-chromatin-interactions
#6
Kush Dalal, Meixia Che, Nanette S Que, Aishwariya Sharma, Rendong Yang, Nada Lallous, Hendrik Borgmann, Deniz Ozistanbullu, Ronnie Tse, Fuqiang Ban, Huifang Li, Kevin J Tam, Mani Roshan-Moniri, Eric Leblanc, Martin E Gleave, Daniel T Gewirth, Scott M Dehm, Artem Cherkasov, Paul S Rennie
Human androgen receptor (AR) is a hormone-activated transcription factor that is an important drug-target in the treatment of prostate cancer. Current small molecule AR-antagonists, such as enzalutamide, compete with androgens that bind to the steroid binding pocket of the AR ligand binding domain (LBD). In castration-resistant prostate cancer (CRPC), drug-resistance can manifest through AR-LBD mutations that convert AR-antagonists into agonists, or by expression of AR-variants lacking the LBD. Such treatment resistance underscores the importance of novel ways of targeting the AR...
August 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28756619/prostate-carcinoma-with-amphicrine-features-further-refining-the-spectrum-of-neuroendocrine-differentiation-in-tumours-of-primary-prostatic-origin
#7
Susan Prendeville, Issam Al-Bozom, Eva Compérat, Joan Sweet, Andrew J Evans, Mohamed Ben-Gashir, Ozgur Mete, Theodorus H van der Kwast, Michelle R Downes
OBJECTIVE: The current WHO classification categorises high grade neuroendocrine (NE) carcinomas of the prostate into small cell and large cell types. A distinct form of carcinoma demonstrating synchronous dual exocrine and NE differentiation, termed amphicrine carcinoma, has been described at various other sites, primarily within the gastrointestinal tract. In this study, we describe the clinicopathologic features of a series of metastatic prostatic carcinomas with amphicrine features...
July 30, 2017: Histopathology
https://www.readbyqxmd.com/read/28754673/androgen-receptor-variants-mediate-dna-repair-after-prostate-cancer-irradiation
#8
Yi Yin, Rui Li, Kangling Xu, Sentai Ding, Jeffrey Li, Guemhee Baek, Susmita G Ramanand, Sam Ding, Zhao Liu, Yunpeng Gao, Mohammed S Kanchwala, Xiangyi Li, Ryan Hutchinson, Xihui Liu, Solomon L Woldu, Chao Xing, Neil B Desai, Felix Y Feng, Sandeep Burma, Johann S de Bono, Scott M Dehm, Ram S Mani, Benjamin P C Chen, Ganesh V Raj
In prostate cancer (PCa), androgen deprivation therapy (ADT) enhances the cytotoxic effects of radiotherapy. This effect is associated with weakening of the DNA damage response (DDR) normally supported by the androgen receptor. Since a significant number of patients will fail combined ADT and radiotherapy, we hypothesized that DDR may be driven by androgen receptor splice variants (ARV) induced by ADT. Investigating this hypothesis, we found that ARV increase the clonogenic survival of PCa cells after irradiation in an ADT-independent manner...
July 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28753843/prognostic-value-of-androgen-receptor-splice-variant-7-in-the-treatment-of-castration-resistant-prostate-cancer-with-next-generation-androgen-receptor-signal-inhibition-a-systematic-review-and-meta-analysis
#9
REVIEW
Heng Li, Zhize Wang, Kun Tang, Hui Zhou, Haoran Liu, Libin Yan, Wei Guan, Ke Chen, Hua Xu, Zhangqun Ye
CONTEXT: Androgen receptor splice variant 7 (AR-V7) may be associated with resistance to next-generation androgen receptor signaling (ARS) inhibitors in castration-resistant prostate cancer (CRPC) sensitive to chemotherapy. OBJECTIVE: To evaluate the prognostic value of AR-V7 for prostate specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) among CRPC patients treated with ARS inhibitors or chemotherapy. EVIDENCE ACQUISITION: A search of PubMed, Embase, and Web of Science databases was performed using the keywords "prostate cancer", "prostate tumor", "prostate neoplasm", "prostate carcinoma"; "AR-V7", "AR3", "androgen receptor splicing variant-7" and "androgen receptor-3"...
January 23, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28729398/quercetin-targets-hnrnpa1-to-overcome-enzalutamide-resistance-in-prostate-cancer-cells
#10
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/28723515/understanding-mechanisms-of-resistance-in-metastatic-castration-resistant-prostate-cancer-the-role-of-the-androgen-receptor
#11
REVIEW
Derya Tilki, Edward M Schaeffer, Christopher P Evans
CONTEXT: After initiation of androgen deprivation therapy (ADT), most patients progress to castration-resistant prostate cancer (CRPC) within 2 or 3 yr. In the USA, approximately 67000 men are estimated to have metastatic CRPC. OBJECTIVE: To provide an overview of different mechanisms driving resistance to therapy in metastatic CRPC, with a focus on androgen receptor (AR)-dependent pathways. EVIDENCE ACQUISITION: A Medline search via PubMed was performed using the keywords metastatic castration resistant prostate cancer (mCRPC), castration-resistant, CRPC, prostate cancer, androgen resistance, hormone-refractory, hormone-independent, androgen receptor, and androgen receptor axis...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723513/the-natural-history-and-outcome-predictors-of-metastatic-castration-resistant-prostate-cancer
#12
REVIEW
Robert J van Soest, Jason A Efstathiou, Cora N Sternberg, Bertand Tombal
CONTEXT: Biomarkers for the treatment of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed by clinicians to facilitate treatment decisions. OBJECTIVE: To review current prognostic and predictive biomarkers in mCRPC. EVIDENCE ACQUISITION: We performed a nonsystematic review of the literature from 2004 to August 2016 by searching in Medline. Cross-matching references were used to search for additional articles. We reviewed clinical research and review articles written in the English language...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28722220/developing-new-targeting-strategy-for-androgen-receptor-variants-in-castration-resistant-prostate-cancer
#13
Bin Wang, U-Ging Lo, Kaijie Wu, Payal Kapur, Xiangyang Liu, Jun Huang, Wei Chen, Elizabeth Hernandez, John Santoyo, Shi-Hong Ma, Rey-Chen Pong, Dalin He, Yi-Qiang Cheng, Jer-Tsong Hsieh
The presence of androgen receptor variant 7 (AR-V7) variants becomes a significant hallmark of castration-resistant prostate cancer (CRPC) relapsed from hormonal therapy and is associated with poor survival of CRPC patients because of lacking a ligand-binding domain. Currently, it still lacks an effective agent to target AR-V7 or AR-Vs in general. Here, we showed that a novel class of agents (thailanstatins, TSTs and spliceostatin A analogs) can significantly suppress the expression of AR-V7 mRNA and protein but in a less extent on the full-length AR expression...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#14
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28707844/castration-resistance-prostate-cancer-what-is-in-the-pipeline
#15
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/28705582/polymorphisms-in-sex-steroid-receptors-from-gene-sequence-to-behavior
#16
REVIEW
Donna L Maney
Sex steroid receptors have received much interest as potential mediators of human behaviors and mental disorders. Candidate gene association studies have identified about 50 genetic variants of androgen and estrogen receptors that correlate with human behavioral phenotypes. Because most of these polymorphisms lie outside coding regions, discerning their effect on receptor function is not straightforward. Thus, although discoveries of associations improve our ability to predict risk, they have not greatly advanced our understanding of underlying mechanisms...
July 10, 2017: Frontiers in Neuroendocrinology
https://www.readbyqxmd.com/read/28702748/-splice-variant-ar-v7-is-it-time-for-its-routine-use-as-a-predictive-marker-in-prostate-cancer
#17
REVIEW
I Tsaur, C Becker, P Thelen, F C Roos
Androgen receptor splice variants (AR-Vs), if overexpressed, lack the ligand-binding domain conveying metastasized castration-resistant prostate cancer with a therapeutic resistance to androgen receptor signaling inhibitors. Particularly AR-V7 has recently been proposed as a potential predictive biomarker to identify patients who would probably benefit most from taxane-based cytotoxic treatment. Several assays to substantiate or quantify AR-V7 expression have recently been proposed. However, their broad clinical value is still debatable...
July 12, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28691182/heat-shock-protein-70-inhibitors-suppress-androgen-receptor-expression-in-lncap95-prostate-cancer-cells
#18
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 is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to androgen deprivation therapy, which is termed castration-resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR-V7), one of the causes of CRPC, is correlated with 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/28642838/adaptive-pathways-and-emerging-strategies-overcoming-treatment-resistance-in-castration-resistant-prostate-cancer
#19
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
#20
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
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