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https://www.readbyqxmd.com/read/28736082/differential-proteome-expression-analysis-of-androgen-dependent-and-independent-pathways-in-lncap-prostate-cancer-cells
#1
Seho Cha, Dong Hoon Shin, Jun Ryeong Seok, Jae Kyung Myung
Prostate cancer (PC) is one of the leading causes of cancer death in men. It commonly develops in older males, but the number of younger men diagnosed with the disease has increased in recent years. Hormone therapies, such as chemical and surgical methods that inhibit androgen synthesis or androgen receptor (AR) activation, have been used for advanced disease. However, castration-resistant PC (CRPC), which exhibits androgen-independent mechanisms for activating AR, develops after a few years of such treatment and no therapy is available...
July 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28734980/histone-demethylase-phf8-regulates-hypoxia-signaling-through-hif1%C3%AE-and-h3k4me3
#2
Peterson Kariuki Maina, Peng Shao, Xiongfei Jia, Qi Liu, Shaikamjad Umesalma, Maximo Marin, Donald Long, Samantha Concepción-Román, Hank Heng Qi
Hypoxia through transcription factor HIF1α plays a critical role in cancer development. In prostate cancer, HIF1α interplays with androgen receptor (AR) to contribute to the progression of this disease to its lethal form-castration-resistant prostate cancer (CRPC). Hypoxia upregulates several epigenetic factors including histone demethylase KDM3A which is a critical co-factor of HIF1α. However, how histone demethylases regulate hypoxia signaling is not fully understood. Here, we report that histone demethylase PHF8 plays an essential role in hypoxia signaling...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28733443/direct-metabolic-interrogation-of-dihydrotestosterone-biosynthesis-from-adrenal-precursors-in-primary-prostatectomy-tissues
#3
Charles Dai, Yoon-Mi Chung, Evan Kovac, Ziqi Zhu, Jianneng Li, Cristina Magi-Galluzzi, Andrew J Stephenson, Eric A Klein, Nima Sharifi
Purpose: A major mechanism of castration-resistant prostate cancer (CRPC) involves intratumoral biosynthesis of dihydrotestosterone (DHT) from adrenal precursors. We have previously shown that adrenal-derived androstenedione (AD) is the preferred substrate over testosterone (T) for 5α-reductase expressed in metastatic CRPC, bypassing T as an obligate precursor to DHT. However, the metabolic pathway of adrenal-derived DHT biosynthesis has not been rigorously investigated in the setting of primary disease in the prostate...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#4
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723516/the-molecular-evolution-of-castration-resistant-prostate-cancer
#5
REVIEW
Yvonne Ceder, Anders Bjartell, Zoran Culig, Mark A Rubin, Scott Tomlins, Tapio Visakorpi
CONTEXT: Androgen deprivation therapy (ADT) is the backbone of treatment for advanced prostate cancer. However, castration-resistant prostate cancer (CRPC) nearly invariably develops through a range of different molecular mechanisms accompanied by progression to a more aggressive phenotype. OBJECTIVE: To understand the key molecular mechanisms leading to CRPC and the functional implications of this progression. Understanding molecular evolutionary mechanisms in CRPC is essential for the development of novel curative therapeutic approaches...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723515/understanding-mechanisms-of-resistance-in-metastatic-castration-resistant-prostate-cancer-the-role-of-the-androgen-receptor
#6
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/28723506/biomarkers-for-metastatic-castration-resistant-prostate-cancer-mcrpc-yes-or-no-predictive-and-response-biomarkers-towards-precision-medicine-in-mcrpc
#7
Joaquin Mateo
Advances in drug development and molecular studies for castration-resistant prostate cancer (CRPC) render the possibility of more efficient and precise patient care through the use of predictive, response, and resistance biomarkers. Thorough scrutiny of assay validation and clinical qualification processes for biomarkers in development, ideally in parallel with clinical trials, is critical for the success of personalised medicine in CRPC management.
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28722220/developing-new-targeting-strategy-for-androgen-receptor-variants-in-castration-resistant-prostate-cancer
#8
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 a novel class of agents (thailanstatins, TSTs, 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/28717648/response-detection-of-castrate-resistant-prostate-cancer-to-clinically-utilised-and-novel-treatments-by-monitoring-phospholipid-metabolism
#9
Tim A D Smith, Su M Phyu, Kholoud S Alzyoud, Chih-Chung Tseng
Androgen receptor (AR) activation is the primary driving factor in prostate cancer which is initially responsive to castration but then becomes resistant (castration-resistant prostate cancer (CRPC)). CRPC cells still retain the functioning AR which can be targeted by other therapies. A recent promising development is the use of inhibitors (Epi-1) of protein-protein interaction to inhibit AR-activated signalling. Translating novel therapies into the clinic requires sensitive early response indicators. Here potential response markers are explored...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28698198/abcb1-mediates-cabazitaxel-docetaxel-cross-resistance-in-advanced-prostate-cancer
#10
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/28692046/inhibition-of-the-androgen-receptor-induces-a-novel-tumor-promoter-zbtb46-for-prostate-cancer-metastasis
#11
W-Y Chen, Y-C Tsai, M K Siu, H-L Yeh, C-L Chen, J J Yin, J Huang, Y-N Liu
Current therapeutic regimens for prostate cancer focus on targeting androgen receptor (AR) signaling. However, the AR is a key factor in luminal epithelium differentiation and was shown to have a role as a tumor suppressor. Thus, its inhibition may activate oncogenic pathways that contribute to metastatic castration-resistant prostate cancer (CRPC). Herein, we report a novel tumor promoter, ZBTB46, which is negatively regulated by AR signaling via microRNA (miR)-1-mediated downregulation. ZBTB46 is associated with malignant prostate cancer and is essential for metastasis...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28691182/hsp70-inhibitors-suppress-androgen-receptor-expression-in-lncap95-prostate-cancer-cells
#12
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/28676619/-iv-therapies-for-crpc-the-indication-of-the-new-medicine-from-the-medical-economical-aspect
#13
Atsushi Mizokami, Yoshifumi Kadono, Yasuhide Kitagawa, Kouji Izumi
No abstract text is available yet for this article.
January 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28668854/pca3-silencing-sensitizes-prostate-cancer-cells-to-enzalutamide-mediated-androgen-receptor-blockade
#14
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/28655783/inhibition-of-androgen-receptor-nuclear-localization-and-castration-resistant-prostate-tumor-growth-by-pyrroloimidazole-based-small-molecules
#15
Khalid Z Masoodi, Yadong Xu, Javid A Dar, Kurtis Eisermann, Laura E Pascal, Erica Parrinello, Junkui Ai, Paul A Johnston, Joel B Nelson, Peter Wipf, Zhou Wang
The androgen receptor (AR) is a ligand-dependent transcription factor that controls the expression of androgen-responsive genes.  A key step in androgen action, which is amplified in castration resistant prostate cancer (CRPC), is AR nuclear translocation. Small molecules capable of inhibiting AR nuclear localization could be developed as novel therapeutics for CRPC. We developed a high throughput screen and identified two structurally-related pyrroloimidazoles that could block AR nuclear localization in CRPC cells...
June 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28649893/radium-223-dichloride-for-the-treatment-of-castration-resistant-prostate-cancer-with-symptomatic-bone-metastases
#16
Nicholas J Vogelzang
Castration-resistant prostate cancer (CRPC) is associated with the development of bone metastases, increased mortality, and a reduction in the patient's quality of life (QOL). The management of metastatic CRPC (mCRPC) has rapidly evolved over the past decade, with a number of available therapeutic agents improving overall survival. Radium-223 dichloride (radium-223), the first targeted alpha therapy, improves survival accompanied by QOL benefits with a favorable safety profile. It is approved in over 40 countries for the treatment of patients with CRPC with symptomatic bone metastases and no known visceral metastatic disease...
July 3, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28648378/steroidogenic-metabolism-of-galeterone-reveals-a-diversity-of-biochemical-activities
#17
Mohammad Alyamani, Zhenfei Li, Michael Berk, Jianneng Li, Jingjie Tang, Sunil Upadhyay, Richard J Auchus, Nima Sharifi
Galeterone is a steroidal CYP17A1 inhibitor, androgen receptor (AR) antagonist, and AR degrader, under evaluation in a phase III clinical trial for castration-resistant prostate cancer (CRPC). The A/B steroid ring (Δ(5),3β-hydroxyl) structure of galeterone is identical to that of cholesterol, which makes endogenous steroids with the same structure (e.g., dehydroepiandrosterone and pregnenolone) substrates for the enzyme 3β-hydroxysteroid dehydrogenase (3βHSD). We found that galeterone is metabolized by 3βHSD to Δ(4)-galeterone (D4G), which is further converted by steroid-5α-reductase (SRD5A) to 3-keto-5α-galeterone (5αG), 3α-OH-5α-galeterone, and 3β-OH-5α-galeterone; in vivo it is also converted to the three corresponding 5β-reduced metabolites...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28646594/prevalence-and-prognosis-of-low-volume-oligorecurrent-hormone-sensitive-prostate-cancer-amenable-to-lesion-ablative-therapy
#18
Aurélie De Bruycker, Bieke Lambert, Tom Claeys, Louke Delrue, Chamberlain Mbah, Gert De Meerleer, Geert Villeirs, Filip De Vos, Kathia De Man, Karel Decaestecker, Valérie Fonteyne, Nicolaas Lumen, Filip Ameye, Ignace Billiet, Steven Joniau, Friedl Vanhaverbeke, Wim Duthoy, Piet Ost
OBJECTIVES: To describe the anatomical patterns of PCa recurrence following primary therapy and investigate if patients with low-volume disease have a better prognosis as compared to their counterparts. MATERIAL AND METHODS: Patients eligible for a F18-choline PET-CT were entered in a prospective cohort study. Eligible patients had an asymptomatic biochemical recurrence following primary PCa treatment and testosterone levels >50 ng/ml. The number of lesions were counted per scan...
June 24, 2017: BJU International
https://www.readbyqxmd.com/read/28645941/a-first-time-in-human-study-of-gsk2636771-a-phosphoinositide-3-kinase-beta-selective-inhibitor-in-patients-with-advanced-solid-tumors
#19
Joaquin Mateo, Gopinath Ganji, Charlotte Lemech, Howard A Burris, Sae-Won Han, Karen E Swales, Shaun Decordova, Maurice P DeYoung, Deborah A Smith, Shanker Kalyana-Sundaram, Jiuhua Wu, Monica Motwani, Rakesh Kumar, Jerry M Tolson, Sun Young Rha, Hyun Cheol Chung, Joseph Paul Eder, Sunil Sharma, Yung-Jue Bang, Jeffrey R Infante, Li Yan, Johann S de Bono, Hendrik-Tobias Arkenau
The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on and off target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.<br /><br />Experimental Design: <p>We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended Phase II dose (RP2D)...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28642484/mir-100-5p-inhibition-induces-apoptosis-in-dormant-prostate-cancer-cells-and-prevents-the-emergence-of-castration-resistant-prostate-cancer
#20
Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC)...
June 22, 2017: Scientific Reports
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