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https://www.readbyqxmd.com/read/29784740/nccn-guidelines-updates-prostate-cancer-and-prostate-cancer-early-detection
#1
Peter H Carroll, James L Mohler
Peter H. Carroll, MD, MPH, and James L. Mohler, MD, updated attendees on what is new in the 2018 NCCN Guidelines for Prostate Cancer Early Detection and for Prostate Cancer, respectively. Their presentations touched on new screening recommendations, shared decision-making, risk stratification, the role of genomic and molecular testing, active surveillance, and newer systemic treatments.
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29779563/association-of-polygenic-risk-scores-for-multiple-cancers-in-a-phenome-wide-study-results-from-the-michigan-genomics-initiative
#2
Lars G Fritsche, Stephen B Gruber, Zhenke Wu, Ellen M Schmidt, Matthew Zawistowski, Stephanie E Moser, Victoria M Blanc, Chad M Brummett, Sachin Kheterpal, Gonçalo R Abecasis, Bhramar Mukherjee
Health systems are stewards of patient electronic health record (EHR) data with extraordinarily rich depth and breadth, reflecting thousands of diagnoses and exposures. Measures of genomic variation integrated with EHRs offer a potential strategy to accurately stratify patients for risk profiling and discover new relationships between diagnoses and genomes. The objective of this study was to evaluate whether polygenic risk scores (PRS) for common cancers are associated with multiple phenotypes in a phenome-wide association study (PheWAS) conducted in 28,260 unrelated, genotyped patients of recent European ancestry who consented to participate in the Michigan Genomics Initiative, a longitudinal biorepository effort within Michigan Medicine...
May 17, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29777112/micrornas-as-potential-therapeutics-to-enhance-chemosensitivity-in-advanced-prostate-cancer
#3
Hui-Ming Lin, Iva Nikolic, Jessica Yang, Lesley Castillo, Niantao Deng, Chia-Ling Chan, Nicole K Yeung, Eoin Dodson, Benjamin Elsworth, Calan Spielman, Brian Y Lee, Zoe Boyer, Kaylene J Simpson, Roger J Daly, Lisa G Horvath, Alexander Swarbrick
Docetaxel and cabazitaxel are taxane chemotherapy treatments for metastatic castration-resistant prostate cancer (CRPC). However, therapeutic resistance remains a major issue. MicroRNAs are short non-coding RNAs that can silence multiple genes, regulating several signalling pathways simultaneously. Therefore, synthetic microRNAs may have therapeutic potential in CRPC by regulating genes involved in taxane response and minimise compensatory mechanisms that cause taxane resistance. To identify microRNAs that can improve the efficacy of taxanes in CRPC, we performed a genome-wide screen of 1280 microRNAs in the CRPC cell lines PC3 and DU145 in combination with docetaxel or cabazitaxel treatment...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773553/intratumoral-androgen-levels-are-linked-to-tmprss2-erg-fusion-in-prostate-cancer
#4
Matias Knuuttila, Arfa Mehmood, Jenni Mäki-Jouppila, Henrik Ryberg, Pekka Taimen, Juha Knaapila, Otto Ettala, Peter J Bostrom, Claes Ohlsson, Mikko S Venäläinen, Asta Laiho, Laura L Elo, Petra Sipilä, Sari Makela, Matti Poutanen
Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral DHT concentrations were significantly higher in the cancerous tissues compared to benign prostate (p<0...
May 17, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29769196/an-in-vivo-screen-identifies-pygo2-as-a-driver-for-metastatic-prostate-cancer
#5
Xin Lu, Xiaolu Pan, Chang-Jiun Wu, Di Zhao, Shan Feng, Yong Zang, Rumi Lee, Sunada Khadka, Samirkumar B Amin, Eun-Jung Jin, Xiaoying Shang, Pingna Deng, Yanting Luo, William R Morgenlander, Jacqueline Weinrich, Xuemin Lu, Shan Jiang, Qing Chang, Nora M Navone, Patricia Troncoso, Ronald A DePinho, Y Alan Wang
Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29767255/bioinformatic-analyses-reveal-the-key-pathways-and-genes-in-the-cxcr4-mediated-mesenchymal-subtype-of-glioblastoma
#6
Li Yi, Luqing Tong, Tao Li, Long Hai, Iruni Roshanie Abeysekera, Zhennan Tao, Haiwen Ma, Peidong Liu, Yang Xie, Jiabo Li, Feng Yuan, Shengping Yu, Xuejun Yang
Glioblastoma multiforme (GBM) is one of the most lethal types of tumour, despite severe treatment methods. The Cancer Genome Atlas has categorised GBMs into proneural, neural, classical and mesenchymal subtypes; the mesenchymal subgroup has the worst prognosis. CXCR4 has been reported as selectively overexpressed in the mesenchymal subtype and positively associated with MES markers. However, to the best of our knowledge the underlying mechanisms regarding how CXCR4 may regulate mesenchymal GBM are still unknown...
May 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29762619/isolation-and-genome-sequencing-of-individual-circulating-tumor-cells-using-hydrogel-encapsulation-and-laser-capture-microdissection
#7
Emily S Park, Justin P Yan, Richard A Ang, Jeong Hyun Lee, Xiaoyan Deng, Simon P Duffy, Kevin Beja, Matti Annala, Peter C Black, Kim N Chi, Alexander W Wyatt, Hongshen Ma
Circulating tumor cells (CTCs) are malignant cells released into the bloodstream with the potential to form metastases in secondary sites. These cells, acquired non-invasively, represent a sample of highly relevant tumor tissue that is an alternative to difficult and low-yield tumor biopsies. In recent years, there has been growing interest in genomic profiling of CTCs to enable longitudinal monitoring of the tumor's adaptive response to therapy. However, due to their extreme rarity, genotyping CTCs has proved challenging...
May 15, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29761524/the-24th-annual-prostate-cancer-foundation-scientific-retreat-report
#8
REVIEW
Andrea K Miyahira, Howard R Soule
INTRODUCTION: The 24th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 5-7, 2017, at the Omni Shoreham Hotel in Washington, DC. METHODS: The PCF Scientific Retreat is a scientific conference that specifically focuses on cutting edge research deemed to have significant promise for accelerating advances in prostate cancer biology and treatment. RESULTS: Themes highlighted at this year's meeting included: (i) new understandings in prostate cancer biology and disease progression; (ii) new mechanisms and treatment targets in advanced prostate cancer; (iii) advances in precision medicine genomics, germline genetics, and selection of targeted therapies; (iv) PSMA-targeted agents for PET imaging and radionuclide therapy; (v) approaches for improving the efficacy of immunotherapy in prostate cancer; (vi) applications of 3D Genomics in prostate cancer research; and (vii) potential applications of artificial intelligence in prostate cancer...
May 15, 2018: Prostate
https://www.readbyqxmd.com/read/29760221/development-and-validation-of-a-prostate-cancer-genomic-signature-that-predicts-early-adt-treatment-response-following-radical-prostatectomy
#9
Mohammed Alshalalfa, R Jeffrey Karnes, Vidit Sharma, Voleak Choeurng, Hussam Al-Deen Ashab, Nicholas Erho, Bruce J Trock, Ashley E Ross, Kasra Yousefi, Harrison K Tsai, Shuang G Zhao, Jeffrey J Tosoian, Zaid Haddad, Mandeep Takhar, S Laura Chang, Daniel E Spratt, Firas Abdollah, Robert B Jenkins, Eric A Klein, Paul L Nguyen, Adam P Dicker, Robert B Den, Elai Davicioni, Felix Y Feng, Tamara L Lotan, Edward M Schaeffer
PURPOSE: Currently no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy (RP) for high risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT. EXPERIMENTAL DESIGN: A training set consisting of 284 RP patients was established after 1:1 propensity score matching metastasis between adjuvant-ADT(a-ADT) treated and no-ADT treated groups...
May 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#10
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
https://www.readbyqxmd.com/read/29755696/the-use-of-long-non-coding-rnas-as-prognostic-biomarkers-and-therapeutic-targets-in-prostate-cancer
#11
REVIEW
Cristian Arriaga-Canon, Inti Alberto De La Rosa-Velázquez, Rodrigo González-Barrios, Rogelio Montiel-Manríquez, Diego Oliva-Rico, Francisco Jiménez-Trejo, Carlo Cortés-González, Luis A Herrera
Prostate cancer is the most common cancer in men and the second leading cause of cancer-related deaths. The most used biomarker to detect prostate cancer is Prostate Specific Antigen (PSA), whose levels are measured in serum. However, it has been recently established that molecular markers of cancer should not be based solely on genes and proteins but should also reflect other genomic traits; long non-coding RNAs (lncRNAs) serve this purpose. lncRNAs are transcripts of >200 bases that do not encode proteins and that have been shown to display abnormal expression profiles in different types of cancer...
April 17, 2018: Oncotarget
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
#12
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/29748182/a-pdx-organoid-biobank-of-advanced-prostate-cancers-captures-genomic-and-phenotypic-heterogeneity-for-disease-modeling-and-therapeutic-screening
#13
Michael L Beshiri, Caitlin M Tice, Crystal Tran, Holly M Nguyen, Adam G Sowalsky, Supreet Agarwal, Keith H Jansson, Qi Yang, Kerry A McGowen, Juan Juan Yin, Aian Neil Alilin, Fatima H Karzai, William Dahut, Eva Corey, Kathleen Kelly
PURPOSE: Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models   that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29740534/genomic-dna-methylation-derived-algorithm-enables-accurate-detection-of-malignant-prostate-tissues
#14
Erfan Aref-Eshghi, Laila C Schenkel, Peter Ainsworth, Hanxin Lin, David I Rodenhiser, Jean-Claude Cutz, Bekim Sadikovic
Introduction: The current methodology involving diagnosis of prostate cancer (PCa) relies on the pathology examination of prostate needle biopsies, a method with high false negative rates partly due to temporospatial, molecular, and morphological heterogeneity of prostate adenocarcinoma. It is postulated that molecular markers have a potential to assign diagnosis to a considerable portion of undetected prostate tumors. This study examines the genome-wide DNA methylation changes in PCa in search of genomic markers for the development of a diagnostic algorithm for PCa screening...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29739972/cell-type-specific-expression-of-oncogenic-and-tumor-suppressive-micrornas-in-the-human-prostate-and-prostate-cancer
#15
Binod Kumar, Avi Z Rosenberg, Su Mi Choi, Karen Fox-Talbot, Angelo M De Marzo, Larisa Nonn, W Nathaniel Brennen, Luigi Marchionni, Marc K Halushka, Shawn E Lupold
MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29732281/imaging-for-the-selection-and-monitoring-of-men-on-active-surveillance-for-prostate-cancer
#16
REVIEW
Maria C Velasquez, Nachiketh Soodana Prakash, Vivek Venkatramani, Bruno Nahar, Sanoj Punnen
Traditional prostate imaging is fairly limited, and only a few imaging modalities have been used for this purpose. Until today, grey scale ultrasound was the most widely used method for the characterization of the prostatic gland, however its limitations for prostate cancer (PCa) detection are well known and hence ultrasound is primarily used to localize the prostate and facilitate template prostate biopsies. In the past decade, multiparametric magnetic resonance imaging (mpMRI) of the prostate has emerged as a promising tool for the detection of PCa...
April 2018: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29727322/unfavorable-pathology-tissue-biomarkers-and-genomic-tests-with-clinical-implications-in-prostate-cancer-management
#17
Jane Kim Nguyen, Cristina Magi-Galluzzi
Prostate cancer management has traditionally relied upon risk stratification of patients based on Gleason score, pretreatment prostate-specific antigen and clinical tumor stage. However, these factors alone do not adequately reflect the inherent complexity and heterogeneity of prostate cancer. Accurate and individualized risk stratification at the time of diagnosis is instrumental to facilitate clinical decision-making and treatment selection tailored to each patient. The incorporation of tissue and genetic biomarkers into current prostate cancer prediction models may optimize decision-making and improve patient outcomes...
May 3, 2018: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/29725504/robust-genomic-copy-number-predictor-of-pan-cancer-metastasis
#18
Alexander Pearlman, Kinnari Upadhyay, Kim Cole, John Loke, Katherine Sun, Susan Fineberg, Stephen J Freedland, Yongzhao Shao, Harry Ostrer
Copy number alterations(CNAs) are the most common genetic changes observed in many cancers, reflecting the innate chromosomal instability of this disorder. Yet, how these alterations affect gene function to promote metastases across different tumor types has not been established. In this study, we developed a pan-cancer metastasis potential score (panMPS) based on observed CNAs. panMPS predicts metastasis and metastasis-free survival in cohorts of patients with prostate cancer, triple negative breast cancer and lung adenocarcinoma, and overall survival in the Metabric breast cancer cohort and three cohorts from The Cancer Genome Atlas (TCGA), including prostate, breast and lung adenocarcinoma...
January 2018: Genes & Cancer
https://www.readbyqxmd.com/read/29721051/lncrna-pcat1-and-its-genetic-variant-rs1902432-are-associated-with-prostate-cancer-risk
#19
Qinbo Yuan, Haiyan Chu, Yuqiu Ge, Gaoxiang Ma, Mulong Du, Meilin Wang, Zhengdong Zhang, Wei Zhang
Emerging evidence has showed that lncRNAs and trait-associated loci in lncRNAs play a crucial role in the progression of cancer including prostate cancer (PCa).This study aimed to investigate the molecular mechanisms of lncRNA PCAT1 involved in PCa development and its genetic variant associated with PCa risk. We applied cell proliferation and apoptosis assays to assess the effect of PCAT1 on PCa cell phenotypes. In addition, the genome-wide profiling of gene expression was assessed from three pairs of DU145 cells transfected with PCAT1 overexpression vector or negative control (NC) vector...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29715200/traf4-mediated-ubiquitination-of-ngf-receptor-trka-regulates-prostate-cancer-metastasis
#20
Ramesh Singh, Dileep Karri, Hong Shen, Jiangyong Shao, Subhamoy Dasgupta, Shixia Huang, Dean P Edwards, Michael M Ittmann, Bert W O'Malley, Ping Yi
Receptor tyrosine kinases (RTKs) are important drivers of cancers. In addition to genomic alterations, aberrant activation of wild type RTKs plays an important role in driving cancer progression. However, the underlying mechanisms of how RTKs drive prostate cancer remain incompletely characterized. Here we show that non-proteolytic ubiquitination of RTK regulates its kinase activity and contributes to RTK-mediated prostate cancer metastasis. TRAF4, an E3 ubiquitin ligase, is highly expressed in metastatic prostate cancer...
May 1, 2018: Journal of Clinical Investigation
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