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https://www.readbyqxmd.com/read/28917268/targeting-androgen-independent-pathways-new-chances-for-patients-with-prostate-cancer
#1
REVIEW
C Cattrini, E Zanardi, G Vallome, A Cavo, L Cerbone, A Di Meglio, C Fabbroni, M M Latocca, F Rizzo, C Messina, A Rubagotti, P Barboro, F Boccardo
Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer (PC). Most patients eventually progress to a condition known as castration-resistant prostate cancer (CRPC), characterized by lack of response to ADT. Although new androgen receptor signaling (ARS) inhibitors and chemotherapeutic agents have been introduced to overcome resistance to ADT, many patients progress because of primary or acquired resistance to these agents. This comprehensive review aims at exploring the mechanisms of resistance and progression of PC, with specific focus on alterations which lead to the activation of androgen receptor (AR)-independent pathways of survival...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#2
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony Michael Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28910332/concurrent-treatment-with-simvastatin-and-nf-%C3%AE%C2%BAb-inhibitor-in-human-castration-resistant-prostate-cancer-cells-exerts-synergistic-anti-cancer-effects-via-control-of-the-nf-%C3%AE%C2%BAb-lin28-let-7-mirna-signaling-pathway
#3
Minyong Kang, Kyoung-Hwa Lee, Hye Sun Lee, Chang Wook Jeong, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak
We examined the anti-cancer effects and molecular mechanism of simvastatin in human castration-resistant prostate cancer (CRPC) cells, particularly focused on LIN28B and its target molecule, let-7 microRNA (miRNA) among the various target genes of NF-κB. A human CRPC cell line (PC3) was used in the current study. Gene expression patterns were evaluated using real time-PCR and western blot analysis. CCK-8 assay was used for assessing cell viability and proliferation, and a clonogenic assay was adopted to evaluate clonal proliferative capabilities...
2017: PloS One
https://www.readbyqxmd.com/read/28906339/multiparametric-magnetic-resonance-imaging-of-prostate-cancer-bone-disease-correlation-with-bone-biopsy-histological-and-molecular-features
#4
Raquel Perez-Lopez, Daniel Nava Rodrigues, Ines Figueiredo, Joaquin Mateo, David J Collins, Dow-Mu Koh, Johann S de Bono, Nina Tunariu
OBJECTIVES: The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases. MATERIALS AND METHODS: Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations...
September 12, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28903426/the-prognostic-implication-of-intraductal-carcinoma-of-the-prostate-in-metastatic-castration-resistant-prostate-cancer-and-its-potential-predictive-value-in-those-treated-with-docetaxel-or-abiraterone-as-first-line-therapy
#5
Jinge Zhao, Pengfei Shen, Guangxi Sun, Ni Chen, Jiandong Liu, Xin Tang, Rui Huang, Diming Cai, Jing Gong, Xingming Zhang, Zhibin Chen, Xiang Li, Qiang Wei, Peng Zhang, Zhenhua Liu, Jiyan Liu, Hao Zeng
Intraductal carcinoma of the prostate (IDC-P) is recognized as a newly pathological entity in 2016 WHO classification. It's role in metastatic castration-resistant prostate cancer (CRPC) remains obscure. We aimed to explore the association of IDC-P with clinical outcome and to further identify its potential predictive role in making first-line treatment decisions for mCRPC. We retrospectively analyzed data of 131 mCRPC patients. IDC-P was diagnosed by re-biopsy at the time of mCRPC. Among total patients, 45 and 41 received abiraterone or docetaxel as first-line therapies, respectively...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903374/resveratrol-enhances-polyubiquitination-mediated-arv7-degradation-in-prostate-cancer-cells
#6
Sarah Wilson, Lucia Cavero, Dali Tong, Qiuli Liu, Kyla Geary, Nicholas Talamonti, Jing Xu, Junjiang Fu, Jun Jiang, Dianzheng Zhang
Although androgen deprivation therapy (ADT) serves as the primary treatment option for localized or metastatic prostate cancer, most cases eventually develop into castration-resistant prostate cancer (CRPC). However, androgen receptor (AR) continues to be functional in CRPC through various mechanisms, including the development of AR splicing variants, especially ARV7. Since it lacks the ligand binding domain but retains the intact DNA binding domain, ARV7 is constitutively active, which makes ARV7-positive prostate cancer responsive to neither abiraterone nor enzalutamide...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901514/multimodal-actions-of-the-phytochemical-sulforaphane-suppress-both-ar-and-ar-v7-in-22rv1-cells-advocating-a-potent-pharmaceutical-combination-against-castration-resistant-prostate-cancer
#7
Namrata Khurana, Hogyoung Kim, Partha K Chandra, Sudha Talwar, Pankaj Sharma, Asim B Abdel-Mageed, Suresh C Sikka, Debasis Mondal
Prostate cancer (PCa) cells expressing full-length androgen receptor (AR-FL) are susceptible to androgen deprivation therapy (ADT). However, outgrowth of castration-resistant prostate cancer (CRPC) can occur due to the expression of constitutively active (ligand-independent) AR splice variants, particularly AR-V7. We previously demonstrated that sulforaphane (SFN), an isothiocyanate phytochemical, can decrease AR-FL levels in the PCa cell lines, LNCaP and C4-2B. Here, we examined the efficacy of SFN in targeting both AR-FL and AR-V7 in the CRPC cell line, CWR22Rv1 (22Rv1)...
August 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28901445/identification-of-genes-associated-with-castration%C3%A2-resistant-prostate-cancer-by-gene-expression-profile-analysis
#8
Chui Guo Huang, Feng Xi Li, Song Pan, Chang Bao Xu, Jun Qiang Dai, Xing Hua Zhao
Prostate cancer (CaP) is a serious and common genital tumor. Generally, men with metastatic CaP can easily develop castration‑resistant prostate cancer (CRPC). However, the pathogenesis and tumorigenic pathways of CRPC remain to be elucidated. The present study performed a comprehensive analysis on the gene expression profile of CRPC in order to determine the pathogenesis and tumorigenic of CRPC. The GSE33316 microarray, which consisted of 5 non‑castrated samples and 5 castrated samples, was downloaded from the gene expression omnibus database...
September 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899970/targeting-prostate-cancer-subtype-1-by-forkhead-box-m1-pathway-inhibition
#9
Kirsi Ketola, Ravi Sn Munuganti, Alastair Davies, Ka Mun Nip, Jennifer L Bishop, Amina Zoubeidi
PURPOSE: Prostate cancer was recently classified to three clinically relevant subtypes (PCS) demarcated by unique pathway activation and clinical aggressiveness. In this preclinical study, we investigated molecular targets and therapeutics for PCS1, the most aggressive and lethal subtype with no treatment options available in the clinic. EXPERIMENTAL DESIGN: We utilized the PCS1 gene set and our model of enzalutamide (ENZR) castration-resistant prostate cancer (CRPC) to identify targetable pathways and inhibitors for PCS1...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28898532/immunological-efficacy-of-herbal-medicines-in-prostate-cancer-patients-treated-by-personalized-peptide-vaccine
#10
Noriko Koga, Fukuko Moriya, Kayoko Waki, Akira Yamada, Kyogo Itoh, Masanori Noguchi
This randomized phase II study investigated the immunological efficacy of herbal medicines (HMs) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HMs or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for the eight-time subcutaneous injection of PPV according to the patient's human leukocyte antigen type and levels of antigen-specific immunoglobulin G (IgG) titer before PPV treatment...
September 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28886115/androgen-receptor-mediated-downregulation-of-microrna-221-and-222-in-castration-resistant-prostate-cancer
#11
Bin Gui, Chen-Lin Hsieh, Philip W Kantoff, Adam S Kibel, Li Jia
MicroRNAs (miRNAs) play important roles in cancer formation and progression by suppressing the production of key functional proteins at the post-transcriptional level in a sequence-specific manner. While differential expression of miRNAs is widely observed in cancers including prostate cancer (PCa), how these miRNAs are transcriptionally regulated is largely unknown. MiRNA-221 and miRNA-222 (miR-221/-222) are well-established oncogenes and overexpressed in breast, liver, pancreas, and lung cancer, but their expression and biological functions in PCa remain controversial...
2017: PloS One
https://www.readbyqxmd.com/read/28885333/rapidly-decreasing-level-of-prostate-specific-antigen-during-initial-androgen-deprivation-therapy-is-a-risk-factor-for-early-progression-to-castration-resistant-prostate-cancer-a-retrospective-study
#12
Guangjie Ji, Gang Song, Cong Huang, Shiming He, Liqun Zhou
To build a practical model for predicting the progression to castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT).In all, 185 patients with prostate cancer who had received ADT as the primary therapy at our institution, from 2003 to 2014, were retrospectively enrolled. The following clinical variables were included in the analysis: age, clinical tumor, node, metastasis stage, Gleason score, risk groups of prostate cancer, prostate-specific antigen (PSA) at the initiation of ADT, PSA nadir after ADT, velocity of PSA decline, and the time to PSA nadir...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28870860/does-early-psadt-epsadt-after-radical-prostatectomy-calculated-prior-to-psa-recurrence-correlate-with-prostate-cancer-outcomes-a-report-from-the-search-database-group
#13
Anna E Teeter, Kagan Griffin, Lauren E Howard, William J Aronson, Martha K Terris, Christopher J Kane, Christopher L Amling, Matthew R Cooperberg, Stephen J Freedland
PURPOSE: Short PSA doubling time (PSADT) following recurrence after radical prostatectomy (RP) portends a poor prognosis. PSADT is traditionally calculated using PSA values >0.2ng/ml. We determined if early PSADT (ePSADT), calculated from the first detectable post-operative PSA up to and including the first recurrence value, correlates with prostate cancer outcomes. METHODS: Cox models were used to examine the association between ePSADT and castration-resistant prostate cancer (CRPC), metastases, all-cause mortality (ACM), and prostate-cancer specific mortality (PCSM) in 674 men who underwent RP between 1988 and 2014...
September 1, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28866255/novel-junction-specific-and-quantifiable-in-situ-detection-of-ar-v7-and-its-clinical-correlates-in-metastatic-castration-resistant-prostate-cancer
#14
Yezi Zhu, Adam Sharp, Courtney M Anderson, John L Silberstein, Maritza Taylor, Changxue Lu, Pei Zhao, Angelo M De Marzo, Emmanuel S Antonarakis, Mindy Wang, Xingyong Wu, Yuling Luo, Nan Su, Daniel Nava Rodrigues, Ines Figueiredo, Jonathan Welti, Emily Park, Xiao-Jun Ma, Ilsa Coleman, Colm Morrissey, Stephen R Plymate, Peter S Nelson, Johann S de Bono, Jun Luo
BACKGROUND: Androgen receptor splice variant 7 (AR-V7) has been implicated in resistance to abiraterone and enzalutamide treatment in men with metastatic castration-resistant prostate cancer (mCRPC). Tissue- or cell-based in situ detection of AR-V7, however, has been limited by lack of specificity. OBJECTIVE: To address current limitations in precision measurement of AR-V7 by developing a novel junction-specific AR-V7 RNA in situ hybridization (RISH) assay compatible with automated quantification...
August 30, 2017: European Urology
https://www.readbyqxmd.com/read/28865178/inhibition-of-il-6-jak-stat3-signaling-in-castration-resistant-prostate-cancer-cells-enhances-the-nk-cell-mediated-cytotoxicity-via-alteration-of-pd-l1-nkg2d-ligand-levels
#15
LiJun Xu, XiaoDong Chen, MingJing Shen, Dong-Rong Yang, Laifu Fang, Guobin Weng, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
To investigate whether IL-6 signaling affects the susceptibility of castration resistant prostate cancer (CRPC) cells to cytotoxic action of natural killer (NK) cells, CRPC cell lines (having different IL-6 level) were developed by lentiviral transduction. While observing no secreted IL-6 level in parental C4-2 and CWR22Rv1 cells, we found the IL-6 expression/secretion in these cells was induced after the transduction process and the IL-6 level difference in C4-2siIL-6/sc and CWR22siIL-6/sc cell CRPC cell sets could be detected...
September 2, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28855993/treatment-sequence-in-castration-resistant-prostate-cancer-a-retrospective-study-in-the-new-anti-androgen-era
#16
Senji Hoshi, Kenji Numahata, Kunio Ono, Nobuhiro Yasuno, Vladimir Bilim, Kiyotsugu Hoshi, Hiroshi Amemiya, Isoji Sasagawa, Shoichiro Ohta
In recent years, abiraterone acetate (AA) and enzalutamide (EZL) have become available for the treatment of cancer. Prior clinical trials have demonstrated the benefits of these agents in males with castration-resistant prostate cancer (CRPC). The optimal sequencing of available therapies in the context of efficacy and known cross-resistance remains uncertain. Based on the mechanisms of action and accessible clinical data, AA and EZL may be indicated for the early stages of prostate cancer. Until clinical trials are conducted to determine the best treatment sequence, individualized therapy is required for each patient based on the clinicopathological characteristics...
October 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28851578/moving-towards-precision-urologic-oncology-targeting-enzalutamide-resistant-prostate-cancer-and-mutated-forms-of-the-androgen-receptor-using-the-novel-inhibitor-darolutamide-odm-201
#17
Hendrik Borgmann, Nada Lallous, Deniz Ozistanbullu, Eliana Beraldi, Naman Paul, Kush Dalal, Ladan Fazli, Axel Haferkamp, Pascale Lejeune, Artem Cherkasov, Martin E Gleave
Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist with a chemical structure distinctly different from currently approved AR antagonists that targets both wild-type and mutated ligand binding domain variants to inhibit AR nuclear translocation. Here, we evaluate the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer (CRPC) as well as in AR mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide. Darolutamide significantly inhibited cell growth and AR transcriptional activity in enzalutamide-resistant MR49F cells in vitro, and led to decreased tumor volume and serum prostate-specific antigen levels in vivo, prolonging survival in mice bearing enzalutamide-resistant MR49F xenografts...
August 26, 2017: European Urology
https://www.readbyqxmd.com/read/28844715/manumycin-a-suppresses-exosome-biogenesis-and-secretion-via-targeted-inhibition-of-ras-raf-erk1-2-signaling-and-hnrnp-h1-in-castration-resistant-prostate-cancer-cells
#18
Amrita Datta, Hogyoung Kim, Madhu Lal, Lauren McGee, Adedoyin Johnson, Ahmed A Moustafa, Jennifer C Jones, Debasis Mondal, Marc Ferrer, Asim B Abdel-Mageed
Emerging evidence links exosomes to cancer progression by the trafficking of oncogenic factors and neoplastic reprogramming of stem cells. This necessitates identification and integration of functionally validated exosome-targeting therapeutics into current cancer management regimens. We employed quantitative high throughput screen on two libraries to identify exosome-targeting drugs; a commercially available collection of 1280 pharmacologically active compounds and a collection of 3300 clinically approved compounds...
August 24, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28831860/associations-between-statin-use-and-progression-in-men-with-prostate-cancer-treated-with-primary-androgen-deprivation-therapy
#19
Marta Kramer Mikkelsen, Frederik Birkebæk Thomsen, Kasper Drimer Berg, Mary Jarden, Signe Benzon Larsen, Rikke Bølling Hansen, Klaus Brasso
INTRODUCTION: In several observational studies, statin use has been associated with reduced risk of progression and mortality in men with prostate cancer (PCa). The study aim was to investigate the association between statin use at time of PCa diagnosis and time to PCa progression in men with advanced or metastatic PCa receiving androgen deprivation therapy (ADT) as primary treatment. PATIENTS AND METHODS: The study population consisted of all men receiving ADT as primary therapy at two Danish Urological Departments in 2007-2013...
August 23, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28830482/a-retrospective-feasibility-study-of-biweekly-reduced-dose-docetaxel-in-asian-patients-with-castrate-resistant-metastatic-prostate-cancer
#20
Hae Su Kim, Ji Yun Lee, Su Jin Lee, Ho Yeong Lim, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han-Yong Choi, Se Hoon Park
BACKGROUND: The aim of this retrospective study was to evaluate the clinical outcomes of reduced dose, biweekly docetaxel chemotherapy for Korean patients with castrate-resistant prostate cancer (CRPC). METHODS: We retrospectively reviewed the medical records of 48 patients with metastatic CRPC who were treated with a biweekly regimen (intravenous docetaxel 40 mg/m(2) on day 1 plus prednisolone 5 mg twice daily) between 2012 and 2015 at Samsung Medical Center (Seoul, Korea)...
August 22, 2017: BMC Urology
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