keyword
MENU ▼
Read by QxMD icon Read
search

Androgen receptor splice variants

keyword
https://www.readbyqxmd.com/read/29764864/targeting-the-hsp40-hsp70-chaperone-axis-as-a-novel-strategy-to-treat-castration-resistant-prostate-cancer
#1
Michael A Moses, Yeong Sang Kim, Genesis M Rivera-Marquez, Nobu Oshima, Matthew J Watson, Kristin Beebe, Catherine Wells, Sunmin Lee, Abbey D Zuehlke, Hao Shao, William E Bingman, Vineet Kumar, Sanjay Malhotra, Nancy L Weigel, Jason E Gestwicki, Jane Trepel, Leonard M Neckers
Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with heat shock protein 40 (Hsp40)...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29760584/lsd1-inhibition-attenuates-androgen-receptor-v7-splice-variant-activation-in-castration-resistant-prostate-cancer-models
#2
Sergio Regufe da Mota, Sarah Bailey, Rosemary A Strivens, Annette L Hayden, Leon R Douglas, Patrick J Duriez, M Teresa Borrello, Hanae Benelkebir, A Ganesan, Graham Packham, Simon J Crabb
Background: Castrate resistant prostate cancer (CRPC) is often driven by constitutively active forms of the androgen receptor such as the V7 splice variant (AR-V7) and commonly becomes resistant to established hormonal therapy strategies such as enzalutamide as a result. The lysine demethylase LSD1 is a co-activator of the wild type androgen receptor and a potential therapeutic target in hormone sensitive prostate cancer. We evaluated whether LSD1 could also be therapeutically targeted in CRPC models driven by AR-V7...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29748904/androgen-receptor-signaling-in-castration-resistant-prostate-cancer-alters-hyperpolarized-pyruvate-to-lactate-conversion-and-lactate-levels-in-vivo
#3
Niki Zacharias, Jaehyuk Lee, Sumankalai Ramachandran, Sriram Shanmugavelandy, James McHenry, Prasanta Dutta, Steven Millward, Seth Gammon, Eleni Efstathiou, Patricia Troncoso, Daniel E Frigo, David Piwnica-Worms, Christopher J Logothetis, Sankar N Maity, Mark A Titus, Pratip Bhattacharya
PURPOSE: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism, and progression. Often, PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors...
May 10, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29731997/androgen-receptor-a-potential-therapeutic-target-for-glioblastoma
#4
Nomi Zalcman, Tamar Canello, Haim Ovadia, Hanna Charbit, Bracha Zelikovitch, Anat Mordechai, Yakov Fellig, Stav Rabani, Tal Shahar, Alexander Lossos, Iris Lavon
The median survival time of patients with glioblastoma is still poor (14.6 month), partly due to a lack of effective treatment. We have observed that androgen receptor (AR) is amplified in glioblastomas at the DNA, RNA and protein levels. The AR gene was amplified in 27% of glioblastoma specimens from men (n=22) and of 38.2% from women (n=21). AR-RNA was overexpressed (>2.5 fold) in 93% (n=30), and AR-protein was induced (>two fold) in 56% of the glioblastomas samples (n=16). Thirty percent of the glioblastomas (n=21) also expressed a constitutively active AR-splice-variant (AR-V7/AR3) lacking the Ligand-Binding-Domain...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29725990/gene-expression-analysis-of-immunomagnetically-enriched-circulating-tumor-cell-fraction-in-castration-resistant-prostate-cancer
#5
Markéta Škereňová, Veronika Mikulová, Otakar Čapoun, David Švec, Katarína Kološtová, Viktor Soukup, Hana Honová, Tomáš Hanuš, Tomáš Zima
BACKGROUND: Molecular characterization of tumors could be a key to therapeutic decision-making with regards to targeted therapies in castration-resistant prostate cancer (CRPC). A convenient solution may be non-invasive liquid biopsy testing of circulating tumor cells (CTCs). For this reason, CTC-enriched samples obtained by immunomagnetic separation (AdnaTest® ) were studied as a source material for high-throughput gene expression analysis using BioMark™. PATIENTS AND METHODS: CTC-enriched samples from 41 CRPC patients previously determined to be CTC positive using the AdnaTest® were retrospectively re-analysed for androgen receptor (AR) messenger RNA (mRNA), using the updated AdnaTest® ...
May 3, 2018: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29712835/histone-demethylase-jmjd1a-promotes-alternative-splicing-of-ar-variant-7-ar-v7-in-prostate-cancer-cells
#6
Lingling Fan, Fengbo Zhang, Songhui Xu, Xiaolu Cui, Arif Hussain, Ladan Fazli, Martin Gleave, Xuesen Dong, Jianfei Qi
Formation of the androgen receptor splicing variant 7 (AR-V7) is one of the major mechanisms by which resistance of prostate cancer to androgen deprivation therapy occurs. The histone demethylase JMJD1A (Jumonji domain containing 1A) functions as a key coactivator for AR by epigenetic regulation of H3K9 methylation marks. Here, we describe a role for JMJD1A in AR-V7 expression. While JMJD1A knockdown had no effect on full-length AR (AR-FL), it reduced AR-V7 levels in prostate cancer cells. Reexpression of AR-V7 in the JMJD1A-knockdown cells elevated expression of select AR targets and partially rescued prostate cancer cell growth in vitro and in vivo...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29682426/replication-study-androgen-receptor-splice-variants-determine-taxane-sensitivity-in-prostate-cancer
#7
Xiaochuan Shan, Gwenn Danet-Desnoyers, Fraser Aird, Irawati Kandela, Rachel Tsui, Nicole Perfito, Elizabeth Iorns
In 2015, as part of the Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative, we published a Registered Report (Shan et al., 2015) that described how we intended to replicate selected experiments from the paper "Androgen Receptor Splice Variants Determine Taxane Sensitivity in Prostate Cancer" (Thadani-Mulero et al., 2014). Here we report the results of those experiments. Growth of tumor xenografts from two prostate cancer xenograft lines, LuCaP 86.2, which expresses wild-type androgen receptor (AR) and AR variant 567, and LuCaP 23...
2018: PeerJ
https://www.readbyqxmd.com/read/29682197/synthesis-and-anticancer-activity-of-the-derivatives-of-marine-compound-rhizochalin-in-castration-resistant-prostate-cancer
#8
Sergey A Dyshlovoy, Katharina Otte, Kseniya M Tabakmakher, Jessica Hauschild, Tatyana N Makarieva, Larisa K Shubina, Sergey N Fedorov, Carsten Bokemeyer, Valentin A Stonik, Gunhild von Amsberg
Development of resistance to standard therapies complicates treatment of advanced prostate cancer. Alternative splicing variants of the androgen receptor (AR), e.g. AR-V7 can mediate resistance to AR-targeting substances abiraterone and enzalutamide. Semi-synthetic marine natural compound rhizochalinin decreases the expression of AR-V7 in human castration-resistant prostate cancer cells and thus resensitizes cells to enzalutamide. In the current study, we modified the structure of rhizochalin in order to determine structure-activity relationships (SAR) and optimize anticancer properties...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#9
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29606109/neoadjuvant-degarelix-with-or-without-apalutamide-followed-by-radical-prostatectomy-for-intermediate-and-high-risk-prostate-cancer-arneo-a-randomized-double-blind-placebo-controlled-trial
#10
Lorenzo Tosco, Annouschka Laenen, Thomas Gevaert, Isabelle Salmon, Christine Decaestecker, Elai Davicioni, Christine Buerki, Frank Claessens, Johan Swinnen, Karolien Goffin, Raymond Oyen, Wouter Everaerts, Lisa Moris, Gert De Meerleer, Karin Haustermans, Steven Joniau
BACKGROUND: Recent retrospective data suggest that neoadjuvant androgen deprivation therapy can improve the prognosis of high-risk prostate cancer (PCa) patients. Novel androgen receptor pathway inhibitors are nowadays available for treatment of metastatic PCa and these compounds are promising for early stage disease. Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor. The combination of apalutamide with degarelix, an LHRH antagonist, could increase the efficacy compared to degarelix alone...
April 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29572775/development-and-application-of-liquid-biopsies-in-metastatic-prostate-cancer
#11
REVIEW
Gareth J Morrison, Amir Goldkorn
PURPOSE OF REVIEW: Metastatic prostate cancer is a lethal and highly heterogeneous malignancy, associated with a broad spectrum of potentially actionable molecular alterations. In the past decade, disease profiling has expanded to include not only traditional tumor tissue, but also liquid biopsies of cells and genetic material circulating in the blood. These liquid biopsies offer a minimally invasive, repeatable source of tumor material for longitudinal disease profiling but also raise new technical and biological challenges...
March 23, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29535823/overexpression-of-p54-nrb-nono-induces-differential-epha6-splicing-and-contributes-to-castration-resistant-prostate-cancer-growth
#12
Ryuji Yamamoto, Tsuyoshi Osawa, Yusuke Sasaki, Shogo Yamamoto, Motonobu Anai, Kouji Izumi, Yoshihiro Matsumura, Juro Sakai, Hiroyuki Aburatani, Atsushi Mizokami, Tatsuhiko Kodama, Toshiya Tanaka
The non-POU domain-containing octamer binding protein p54nrb /NONO is a multifunctional nuclear protein involved in RNA splicing, processing, and transcriptional regulation of nuclear hormone receptors. Through chromosome copy number analysis via whole-exome sequencing, we revealed amplification of the chromosome Xq11.22-q21.33 locus containing the androgen receptor ( AR ) and NONO genes in androgen-independent, castration-resistant prostate cancer (CRPC)-like LNCaP-SF cells. Moreover, NONO was frequently amplified and overexpressed in patients with CRPC...
February 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29508425/ar-v7-in-circulating-tumor-cells-cluster-as-a-predictive-biomarker-of-abiraterone-acetate-and-enzalutamide-treatment-in-castration-resistant-prostate-cancer-patients
#13
Takatsugu Okegawa, Naoki Ninomiya, Kazuki Masuda, Yu Nakamura, Mitsuhiro Tambo, Kikuo Nutahara
OBJECTIVE: We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide. METHODS: We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay...
June 2018: Prostate
https://www.readbyqxmd.com/read/29500328/digital-circulating-tumor-cell-analyses-for-prostate-cancer-precision-oncology
#14
Ellen Heitzer, Michael R Speicher
<b/> In this issue of Cancer Discovery , Miyamoto and colleagues adapted their microfluidic CTC-iChip isolation platform with a digital RNA-PCR readout for eight prostate-specific transcripts and two assays for the androgen receptor mRNA splice variant ARV7 and the TMPRSS2-ERG translocation transcript. In patients with metastatic castrate-resistant prostate cancer at initiating abiraterone therapy in a first-line setting, the resulting RNA-based digital circulating tumor cell signatures identified patients with a shorter overall survival, and in patients with clinically localized disease, the signatures identified those with seminal vesicle invasion and pelvic lymph node involvement...
March 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29497605/enzalutamide-and-blocking-androgen-receptor-in-advanced-prostate-cancer-lessons-learnt-from-the-history-of-drug-development-of-antiandrogens
#15
REVIEW
Yusuke Ito, Marianne D Sadar
Enzalutamide is a nonsteroidal antiandrogen for the treatment of metastatic castration-resistant prostate cancer (mCRPC) both before and after chemotherapy. Enzalutamide is more effective than its predecessor bicalutamide, which was analyzed in head-to-head studies of patients with CRPC. This family of nonsteroidal antiandrogens is now comprised of four drugs approved by the US Food and Drug Administration with two investigational drugs in clinical trials. Antiandrogens have been employed clinically for more than five decades to provide a rich resource of information...
2018: Research and Reports in Urology
https://www.readbyqxmd.com/read/29474983/an-in-depth-evaluation-of-the-validity-and-logistics-surrounding-the-testing-of-ar-v7-mrna-expression-in-circulating-tumor-cells
#16
Anieta M Sieuwerts, Bianca Mostert, Michelle van der Vlugt-Daane, Jaco Kraan, Corine M Beaufort, Mai Van, Wendy J C Prager, Bram De Laere, Nick Beije, Paul Hamberg, Hans M Westgeest, Metin Tascilar, Luc Y Dirix, Wendy Onstenk, Ronald de Wit, Martijn P Lolkema, Ron H J Mathijssen, John W M Martens, Stefan Sleijfer
Recent reports have emphasized the clinical relevance of detecting AR-V7 in circulating tumor cells (CTCs). Our aim was to set up a validated multicenter pipeline to measure AR-V7 by quantitative RT-PCR (RT-qPCR) in RNA isolated from CellSearch-enriched CTCs to provide an AR-V7-positive or AR-V7-negative score in a clinically acceptable time range. CellSearch-enirched CTCs from patients with metastatic castration-resistant prostate cancer were characterized by RT-qPCR. After optimization, it was prospectively tested whether it was possible to report the AR-V7 status within 11 days (PRELUDE study)...
May 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29453314/ar-expression-in-breast-cancer-ctcs-associates-with-bone-metastases
#17
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia Mackenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
April 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29398263/expression-of-androgen-receptor-splice-variant-7-or-9-in-whole-blood-does-not-predict-response-to-androgen-axis-targeting-agents-in-metastatic-castration-resistant-prostate-cancer
#18
Sarah Q To, Edmond M Kwan, Heidi C Fettke, Andrew Mant, Maria M Docanto, Luciano Martelotto, Patricia Bukczynska, Nicole Ng, Lisa-Jane K Graham, Phillip Parente, Carmel Pezaro, Kate Mahon, Lisa Horvath, Tilman Todenhöfer, Arun A Azad
In 2014, a landmark study was published demonstrating that the expression of androgen receptor splice variant (AR-V) 7 was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumour cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR-Vs and treatment response...
February 2, 2018: European Urology
https://www.readbyqxmd.com/read/29396419/partial-androgen-insensitivity-syndrome-caused-by-a-deep-intronic-mutation-creating-an-alternative-splice-acceptor-site-of-the-ar-gene
#19
Hiroyuki Ono, Hirotomo Saitsu, Reiko Horikawa, Shinichi Nakashima, Yumiko Ohkubo, Kumiko Yanagi, Kazuhiko Nakabayashi, Maki Fukami, Yasuko Fujisawa, Tsutomu Ogata
Although partial androgen insensitivity syndrome (PAIS) is caused by attenuated responsiveness to androgens, androgen receptor gene (AR) mutations on the coding regions and their splice sites have been identified only in <25% of patients with a diagnosis of PAIS. We performed extensive molecular studies including whole exome sequencing in a Japanese family with PAIS, identifying a deep intronic variant beyond the branch site at intron 6 of AR (NM_000044.4:c.2450-42 G > A). This variant created the splice acceptor motif that was accompanied by pyrimidine-rich sequence and two candidate branch sites...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29370587/-the-impact-of-the-androgen-receptor-splice-variant-ar-v7-on-the-prognosis-and-treatment-of-advanced-prostate-cancer
#20
P Thelen, H Taubert, S Duensing, G Kristiansen, A S Merseburger, M V Cronauer
A recently discovered mechanism enabling prostate cancer cells to escape the effects of endocrine therapies consists in the synthesis of C-terminally truncated, constitutively active androgen receptor (AR) splice variants (AR-V). Devoid of a functional C-terminal hormone/ligand binding domain, various AR-Vs are insensitive to therapies targeting the androgen/AR signalling axis. Preliminary studies suggest that AR-V7, the most common AR-V, is a promising predictive tumour marker and a relevant selection marker for the treatment of advanced prostate cancer...
January 25, 2018: Aktuelle Urologie
keyword
keyword
84710
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"