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https://www.readbyqxmd.com/read/29453313/multigene-profiling-of-ctcs-in-mcrpc-identifies-a-clinically-relevant-prognostic-signature
#1
Udit Singhal, Yugang Wang, James Henderson, Yashar S Niknafs, Yuanyuan Qiao, Amy Gursky, Alexander Zaslavsky, Jae-Seung Chung, David C Smith, R Jeffrey Karnes, S Laura Chang, Felix Y Feng, Ganesh S Palapattu, Russell S Taichman, Arul M Chinnaiyan, Scott A Tomlins, Todd M Morgan
The trend towards precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer related genes...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29451339/an-indispensable-role-of-androgen-receptor-in-wnt-responsive-cells-during-prostate-development-maturation-and-regeneration
#2
Yongfeng He, Erika Hooker, Eun-Jeong Yu, Huiqing Wu, Gerald R Cunha, Zijie Sun
Androgen signaling is essential for prostate development, morphogenesis, and regeneration. Emerging evidence indicates that Wnt/β-catenin signaling also contributes to prostate development specifically through regulation of cell fate determination. Prostatic Axin2-expressing cells are able to respond to Wnt signals and possess the progenitor properties to regenerate prostatic epithelium. Despite critical roles of both signaling pathways, the biological significance of androgen receptor (AR) in Axin2-expressing Wnt-responsive cells remains largely unexplored...
February 16, 2018: Stem Cells
https://www.readbyqxmd.com/read/29448139/discovery-and-optimization-of-1-1h-indol-1-yl-ethanone-derivatives-as-cbp-ep300-bromodomain-inhibitors-for-the-treatment-of-castration-resistant-prostate-cancer
#3
Qiuping Xiang, Chao Wang, Yan Zhang, Xiaoqian Xue, Ming Song, Cheng Zhang, Chenchang Li, Chun Wu, Kuai Li, Xiaoyan Hui, Yulai Zhou, Jeff B Smaill, Adam V Patterson, Donghai Wu, Ke Ding, Yong Xu
The CREB (cAMP responsive element binding protein) binding protein (CBP) and its homolog EP300 have emerged as new therapeutic targets for the treatment of cancer and inflammatory diseases. Here we report the identification, optimization and evaluation of 1-(1H-indol-1-yl)ethanone derivatives as CBP/EP300 inhibitors starting from fragment-based virtual screening (FBVS). A cocrystal structure of the inhibitor (22e) in complex with CBP provides a solid structural basis for further optimization. The most potent compound 32h binds to the CBP bromodomain and has an IC 50 value of 0...
February 6, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29445483/lenalidomide-decreased-the-psa-level-for-castration-resistant-prostate-cancer-a-case-report
#4
Kota Shimokihara, Takashi Kawahara, Taisei Suzuki, Taku Mochizuki, Daiji Takamoto, Jun-Ichi Teranishi, Yasuhide Miyoshi, Yasushi Yumura, Masahiro Yao, Hiroji Uemura
Lenalidomide has been developed as the derivative of thalidomide that has fewer side effects. We herein report a rare case of castration-resistant prostate cancer successfully maintained using lenalidomide for multiple myeloma.
February 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29439820/germline-dna-repair-gene-mutations-and-outcomes-in-men-with-metastatic-castration-resistant-prostate-cancer-receiving-first-line-abiraterone-and-enzalutamide
#5
Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Chao Liang, Hao Wang, Yan Chen, John L Silberstein, Danilo Piana, Zhao Lai, Yidong Chen, William B Isaacs, Jun Luo
BACKGROUND: Inherited DNA-repair gene mutations are more prevalent in men with advanced prostate cancer than previously thought, but their clinical implications are not fully understood. OBJECTIVE: To investigate the clinical significance of germline DNA-repair gene alterations in men with metastatic castration-resistant prostate cancer (mCRPC) receiving next-generation hormonal therapy (NHT), with a particular emphasis on BRCA/ATM mutations. DESIGN, SETTING, AND PARTICIPANTS: We interrogated 50 genes for pathogenic or likely pathogenic germline mutations using leukocyte DNA from 172 mCRPC patients beginning treatment with first-line NHT with abiraterone or enzalutamide...
February 10, 2018: European Urology
https://www.readbyqxmd.com/read/29438990/nuclear-receptor-lrh-1-functions-to-promote-castration-resistant-growth-of-prostate-cancer-via-its-promotion-of-intratumoral-androgen-biosynthesis
#6
Lijia Xiao, Yuliang Wang, Kexin Xu, Hao Hu, Zhenyu Xu, Dinglan Wu, Zhu Wang, Wenxing You, Chi-Fai Ng, Shan Yu, Franky Leung Chan
Targeting of steroidogenic enzymes (e.g. abiraterone acetate targeting CYP17A1) has been developed as a novel therapeutic strategy against metastatic castration-resistant prostate cancer (CRPC). However, resistance to steroidal inhibitors inevitably develops in patients, the mechanisms of which remain largely unknown. Liver receptor homolog-1 (LRH-1, NR5A2) is a nuclear receptor, originally characterized as an important regulator of some liver-specific metabolic genes. Here we report that LRH-1, which exhibited an increased expression pattern in high-grade prostate cancer and CRPC xenograft models, functions to promote de novo androgen biosynthesis via its direct transactivation of several key steroidogenic enzyme genes, elevating intratumoral androgen levels and reactivating AR signaling in CRPC xenografts as well as abiraterone-treated CRPC tumors...
February 8, 2018: Cancer Research
https://www.readbyqxmd.com/read/29438723/discovery-and-development-of-odm-204-a-novel-nonsteroidal-compound-for-the-treatment-of-castration-resistant-prostate-cancer-by-blocking-the-androgen-receptor-and-inhibiting-cyp17a1
#7
REVIEW
Riikka Oksala, Anu Moilanen, Reetta Riikonen, Petteri Rummakko, Arja Karjalainen, Mikko Passiniemi, Gerd Wohlfahrt, Päivi Taavitsainen, Chira Malmström, Meri Ramela, Hanna-Maija Metsänkylä, Riikka Huhtaniemi, Pekka J Kallio, Mika Vj Mustonen
We report the discovery of a novel nonsteroidal dual-action compound, ODM-204, that holds promise for treating patients with castration-resistant prostate cancer (CRPC), an advanced form of prostate cancer characterised by high androgen receptor (AR) expression and persistent activation of the AR signaling axis by residual tissue androgens. For ODM-204, has a dual mechanism of action. The compound is anticipated to efficiently dampen androgenic stimuli in the body by inhibiting CYP17A1, the prerequisite enzyme for the formation of dihydrotestosterone (DHT) and testosterone (T), and by blocking AR with high affinity and specificity...
February 10, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29436390/identification-of-galeterone-and-abiraterone-as-inhibitors-of-dehydroepiandrosterone-sulfonation-catalyzed-by-human-hepatic-cytosol-sult2a1-sult2b1b-and-sult1e1
#8
Caleb K Y Yip, Sumit Bansal, Siew Ying Wong, Aik Jiang Lau
Galeterone and abiraterone acetate are anti-androgens developed for the treatment of metastatic castration-resistant prostate cancer. In the present study, we investigated the effect of these drugs on dehydroepiandrosterone (DHEA) sulfonation catalyzed by human liver and intestinal cytosols and human recombinant sulfotransferase enzymes (SULT2A1, SULT2B1b, and SULT2E1), and compared their effects to those of other anti-androgens (cyproterone acetate, spironolactone, and danazol). Each of these chemicals (10 μM) inhibited DHEA sulfonation catalyzed by human liver and intestinal cytosols...
February 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29435052/simvastatin-in-combination-with-meclofenamic-acid-inhibits-the-proliferation-and-migration-of-human-prostate-cancer-pc-3-cells-via-an-akr1c3-mechanism
#9
Yoshitaka Sekine, Hiroshi Nakayama, Yoshiyuki Miyazawa, Haruo Kato, Yosuke Furuya, Seiji Arai, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuto Ito, Kazuhiro Suzuki
Statins have become of interest in research due to their anticancer effects. However, the exact mechanism of their anticancer properties remains unclear. The authors previously reported that statins decrease intracellular cholesterol levels in androgen-independent prostate cancer cells. In de novo androgen synthesis, cholesterol is the primary material and certain enzymes have important roles. The present study aimed to determine whether simvastatin alters the expression of androgen synthesis-associated enzymes in androgen-independent prostate cancer cells...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434990/abiraterone-acetate-withdrawal-syndrome-speculations-on-the-underlying-mechanisms
#10
Tomonori Kato, Akira Komiya, Joji Yuasa, Kanya Kaga, Mayuko Kaga, Satoko Kojima, Yukio Naya, Shigeo Isaka
A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml. Bicalutamide was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434663/natural-history-of-castration-resistant-prostate-cancer-in-sub-saharan-african-black-men-a-single-centre-study-of-nigerian-men
#11
REVIEW
Jibril O Bello
Purpose: Native sub-Saharan African black men (SSBM) are disproportionately impacted by higher stage and incurable forms of prostate cancer (PCa). This study evaluates the natural history and survival of a cohort of SSBM with castration-resistant prostate cancer (CRPC). Methods: A retrospective study of patients with CRPC as defined by the Prostate Cancer Working Group 2 managed at a centre in sub-Saharan Africa between January 2011 and December 2015 was conducted...
2018: Ecancermedicalscience
https://www.readbyqxmd.com/read/29432837/vitamin-k2-a-menaquinone-present-in-dairy-products-targets-castration-resistant-prostate-cancer-cell-line-by-activating-apoptosis-signaling
#12
Subramanyam Dasari, Angela Lincy Prem Antony Samy, Andre Kajdacsy-Balla, Maarten C Bosland, Gnanasekar Munirathinam
The aim of this study was to evaluate the therapeutic effects of vitamin K2 (VK2) on castration-resistant prostate cancer (CRPC) and its anti-cancer mechanisms in a pre-clinical study using a VCaP cell line (ATCC ® CRL-2876™) which was established from a vertebral bone metastasis from a patient with hormone refractory prostate cancer. Our data showed that VK2 significantly inhibited CRPC VCaP cell proliferation in a dosedependent manner at 48 h treatment in vitro. In addition, VK2 reduced the migration potential of VCaP cells and inhibited anchorage-independent growth of these cells...
February 9, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29431639/cxcl12%C3%AE-%C3%A2-promotes-development-of-metastatic-castration-resistant-prostate-cancer-by-induction-of-cancer-stem-cell-and-neuroendocrine-phenotypes
#13
Younghun Jung, Frank C Cackowski, Kenji Yumoto, Ann Decker, Jingcheng Wang, Jinkoo Kim, Eunsohl Lee, Yugang Wang, Jae-Seung Chung, Amy M Gursky, Paul H Krebsbach, Kenneth J Pienta, Todd M Morgan, Russell S Taichman
There is evidence that cancer stem-like cells (CSC) and neuroendocrine (NE) behavior play critical roles in the pathogenesis and clinical course of metastatic castration-resistant prostate cancer (m-CRPC). However, there is limiting mechanistic understanding of how CSC and NE phenotypes impact the development of m-CRPC, which could improve opportunities to identify useful biomarkers and therapeutics. In this study, we explored the role of the intracellular chemokine CXCL12γ in CSC induction and NE differentiation and its impact on m-CRPC...
February 5, 2018: Cancer Research
https://www.readbyqxmd.com/read/29431540/pharmacokinetic-pharmacodynamic-drug-evaluation-of-enzalutamide-for-treating-prostate-cancer
#14
Jeong Hee Hong
Enzalutamide is the first approved second-generation androgen receptor (AR) antagonist in the treatment of metastatic castration-resistant prostate cancer (mCRPC) with or without docetaxel-based chemotherapy. Over the past 5 years, a number of attempts were made to determine the efficacy of enzalutamide in the different clinical settings. Areas covered: A literature search was performed at the PubMed, Embase, and Web of Science database to collect the most relevant and impactful studies, including basic science investigations, clinical trials, and reviews...
February 12, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29431193/circulating-tumor-cells-and-survival-in-abiraterone-and-enzalutamide-treated-patients-with-castration-resistant-prostate-cancer
#15
Bram De Laere, Steffi Oeyen, Peter Van Oyen, Christophe Ghysel, Jozef Ampe, Piet Ost, Wim Demey, Lucien Hoekx, Dirk Schrijvers, Barbara Brouwers, Willem Lybaert, Els Everaert, Piet Van Kerckhove, Daan De Maeseneer, Michiel Strijbos, Alain Bols, Karen Fransis, Nick Beije, Inge de Kruijff, Valerie van Dam, Anja Brouwer, Pieter-Jan van Dam, Gert Van den Eynden, Annemie Rutten, Stefan Sleijfer, Jean Vandebroek, Steven Van Laere, Luc Dirix
BACKGROUND: The outcome to treatment administered to patients with metastatic castration-resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making. OBJECTIVE: To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second-line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies...
February 12, 2018: Prostate
https://www.readbyqxmd.com/read/29429804/clinical-outcome-of-prostate-cancer-patients-with-germline-dna-repair-mutations-retrospective-analysis-from-an-international-study
#16
Joaquin Mateo, Heather H Cheng, Himisha Beltran, David Dolling, Wen Xu, Colin C Pritchard, Helen Mossop, Pasquale Rescigno, Raquel Perez-Lopez, Verena Sailer, Michael Kolinsky, Ada Balasopoulou, Claudia Bertan, David M Nanus, Scott T Tagawa, Heather Thorne, Bruce Montgomery, Suzanne Carreira, Shahneen Sandhu, Mark A Rubin, Peter S Nelson, Johann S de Bono
BACKGROUND: Germline DNA damage repair gene mutation (gDDRm) is found in >10% of metastatic prostate cancer (mPC). Their prognostic and predictive impact relating to standard therapies is unclear. OBJECTIVE: To determine whether gDDRm status impacts benefit from established therapies in mPC. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective, international, observational study. Medical records were reviewed for 390 mPC patients with known gDDRm status...
January 29, 2018: European Urology
https://www.readbyqxmd.com/read/29425687/asc-j9%C3%A2-suppresses-prostate-cancer-cell-invasion-via-altering-the-sumoylation-phosphorylation-of-stat3
#17
WanYing Lin, Jie Luo, Yin Sun, ChangYi Lin, Gonghui Li, Yuanjie Niu, Chawnshang Chang
Unlike the androgen-deprivation therapy (ADT) to either reduce the androgen biosynthesis (for example, Abiraterone) or to prevent binding of androgen to the androgen receptor (AR) (for example, Casodex or Enzalutamide), that may result in the decreasing the prostate cancer (PCa) cell growth yet may also increasing the PCa cell invasion, the recently identified AR degradation enhancer ASC-J9® may function via degrading the AR protein to simultaneously suppress the PCa cell proliferation and invasion. The details of this unique mechanism, however, remain unclear...
February 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29423094/differential-regulation-of-the-androgen-receptor-by-protein-phosphatase-regulatory-subunits
#18
James Grey, Dominic Jones, Laura Wilson, Sirintra Nakjang, Jake Clayton, Richard Temperley, Emma Clark, Luke Gaughan, Craig Robson
The Androgen Receptor (AR) is a key molecule in the development, maintenance and progression of prostate cancer (PC). However, the relationship between the AR and co-regulatory proteins that facilitate AR activity in castrate resistant settings remain understudied. Here we show that protein phosphatase 1 regulatory subunits, identified from a phosphatase RNAi screen, direct PP1 catalytic subunits to a varied yet significant response in AR function. As such, we have characterised the PP1β holoenzyme, myosin phosphatase (MLCP), as a novel ligand independent regulator of the AR...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29423050/enhanced-anti-tumor-efficacy-and-mechanisms-associated-with-docetaxel-piperine-combination-in-vitro-and-in-vivo-investigation-using-a-taxane-resistant-prostate-cancer-model
#19
Chenrui Li, Zhijun Wang, Qian Wang, Rebecca Lucinda Ka Yan Ho, Ying Huang, Moses S S Chow, Christopher Wai Kei Lam, Zhong Zuo
Docetaxel (DTX) is widely used for metastatic castrated resistant prostate cancer, but its efficacy is often compromised by drug resistance associated with low intracellular concentrations. Piperine (PIP) could enhance the bioavailability of other drugs via the inhibition of CYPs and P-gp activities. Thus, we hypothesize a positive effect with the DTX-PIP combination on the anti-tumor efficacy and intra-tumor DTX concentrations in taxane-resistant prostate cancer. ICR-NOD/SCID mice implanted with taxane-resistant human prostate cancer cells were administrated with saline as well as PIP and DTX separately or in combination...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29421982/immune-based-therapies-for-metastatic-prostate-cancer-an-update
#20
Md Kamal Hossain, Kamrun Nahar, Osaana Donkor, Vasso Apostolopoulos
Prostate cancer (PC) is a common malignancy among elderly males and is noncurable once it becomes metastatic. In recent years, a number of antigen-delivery systems have emerged as viable and promising immunotherapeutic agents against PC. The approval of sipuleucel-T by the US FDA for the treatment of males with asymptomatic or minimally symptomatic castrate resistant PC was a landmark in cancer immunotherapy, making this the first approved immunotherapeutic. A number of vaccines are under clinical investigation, each having its own set of advantages and disadvantages...
February 1, 2018: Immunotherapy
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