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https://www.readbyqxmd.com/read/29348142/sema3c-drives-cancer-growth-by-transactivating-multiple-receptor-tyrosine-kinases-via-plexin-b1
#1
James W Peacock, Ario Takeuchi, Norihiro Hayashi, Liangliang Liu, Kevin J Tam, Nader Al Nakouzi, Nastaran Khazamipour, Tabitha Tombe, Takashi Dejima, Kevin Ck Lee, Masaki Shiota, Daksh Thaper, Wilson Cw Lee, Daniel Hf Hui, Hidetoshi Kuruma, Larissa Ivanova, Parvin Yenki, Ivy Zf Jiao, Shahram Khosravi, Alice L-F Mui, Ladan Fazli, Amina Zoubeidi, Mads Daugaard, Martin E Gleave, Christopher J Ong
Growth factor receptor tyrosine kinase (RTK) pathway activation is a key mechanism for mediating cancer growth, survival, and treatment resistance. Cognate ligands play crucial roles in autocrine or paracrine stimulation of these RTK pathways. Here, we show SEMA3C drives activation of multiple RTKs including EGFR, ErbB2, and MET in a cognate ligand-independent manner via Plexin B1. SEMA3C expression levels increase in castration-resistant prostate cancer (CRPC), where it functions to promote cancer cell growth and resistance to androgen receptor pathway inhibition...
January 18, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29346776/loss-of-an-androgen-inactivating-and-isoform-specific-hsd17b4-splice-form-enables-emergence-of-castration-resistant-prostate-cancer
#2
Hyun-Kyung Ko, Michael Berk, Yoon-Mi Chung, Belinda Willard, Rohan Bareja, Mark Rubin, Andrea Sboner, Nima Sharifi
Castration-resistant prostate cancer (CRPC) requires tumors to engage metabolic mechanisms that allow sustained testosterone and/or dihydrotestosterone to stimulate progression. 17β-Hydroxysteroid dehydrogenase type 4 (17βHSD4), encoded by HSD17B4, is thought to inactivate testosterone and dihydrotestosterone by converting them to their respective inert 17-keto steroids. Counterintuitively, HSD17B4 expression increases in CRPC and predicts poor prognosis. Here, we show that, of five alternative splice forms, only isoform 2 encodes an enzyme capable of testosterone and dihydrotestosterone inactivation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29340039/integrative-molecular-network-analysis-identifies-emergent-enzalutamide-resistance-mechanisms-in-prostate-cancer
#3
Carly J King, Josha Woodward, Jacob Schwartzman, Daniel J Coleman, Robert Lisac, Nicholas J Wang, Kathryn Van Hook, Lina Gao, Joshua Urrutia, Mark A Dane, Laura M Heiser, Joshi J Alumkal
Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29336978/metastatic-burden-in-newly-diagnosed-hormone-naive-metastatic-prostate-cancer-comparing-definitions-of-chaarted-and-latitude-trial
#4
Sarah Buelens, Filip Poelaert, Bert Dhondt, Valérie Fonteyne, Pieter De Visschere, Piet Ost, Sofie Verbeke, Geert Villeirs, Kathia De Man, Sylvie Rottey, Karel Decaestecker, Nicolaas Lumen
OBJECTIVES: No uniformity exists in the definition of metastatic burden in metastatic hormone-naive prostate cancer (mHNPC) across clinical trials making their comparison challenging. We explored definition agreement and prognostic significance of bulky mHNPC according to the CHAARTED and LATITUDE trial. MATERIALS AND METHODS: Since 2014, 95 patients with newly diagnosed mHNPC were prospectively registered. For this study, they were categorized as having high-volume (HVD) vs...
January 11, 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29330943/epigenetic-markers-in-circulating-cell-free-dna-as-prognostic-markers-for-survival-of-castration-resistant-prostate-cancer-patients
#5
Rianne J Hendriks, Siebren Dijkstra, Frank P Smit, Johan Vandersmissen, Hendrik Van de Voorde, Peter F A Mulders, Inge M van Oort, Wim Van Criekinge, Jack A Schalken
BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. METHODS: In this prospective study, patients were included before starting new treatment after developing CRPC...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#6
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29323792/the-retinamide-vnlg-152-inhibits-ar-ar-v7-and-mnk-eif4esignaling-pathways-to-suppress-emt-and-castration-resistant-prostate-cancer-xenograft-growth
#7
Vidya P Ramamurthy, Senthilmurugan Ramalingam, Lalji K Gediya, Vincent C O Njar
VNLG-152, a lead novel retinamide (NR) shown to suppress growth and progression in genetically diverse PCa cells via inhibition of AR signaling and eIF4E translational machinery. Herein, we report therapeutic effects of VNLG-152 on castration resistant prostate cancer (CRPC) growth and metastatic phenotype in CRPC tumor xenograft model. Administration of VNLG-152 significantly and dose-dependently suppressed the growth of aggressive CWR22Rv1 tumors by 63.4% and 76.3% respectively (P = 0.001), vs. vehicle with no host toxicity...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29319382/ctc-derived-ar-v7-detection-as-a-prognostic-and-predictive-biomarker-in-advanced-prostate-cancer
#8
Diogo A Bastos, Emmanuel S Antonarakis
Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay has been identified as one of the markers that can be used to predict survival, with added value beyond currently available prognostic factors. Recently, androgen receptor splice variant 7 (AR-V7) detection has been associated with worse outcomes for patients with castration-resistant prostate cancer (CRPC) treated with novel androgen receptor-signaling (ARS) inhibitors such as abiraterone and enzalutamide but not taxane chemotherapies...
January 10, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29314097/effect-of-fak-inhibitor-vs-6063-defactinib-on-docetaxel-efficacy-in-prostate-cancer
#9
Hui-Ming Lin, Brian Y Lee, Lesley Castillo, Calan Spielman, Judith Grogan, Nicole K Yeung, James G Kench, Phillip D Stricker, Anne-Maree Haynes, Margaret M Centenera, Lisa M Butler, S Martin Shreeve, Lisa G Horvath, Roger J Daly
BACKGROUND: Docetaxel, the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC) also enhances the survival of patients with metastatic castration-sensitive prostate cancer (CSPC) when combined with androgen-deprivation therapy. Focal Adhesion Kinase (FAK) activation is a mediator of docetaxel resistance in prostate cancer cells. The aim of this study was to investigate the effect of the second generation FAK inhibitor VS-6063 on docetaxel efficacy in pre-clinical CRPC and CSPC models...
January 5, 2018: Prostate
https://www.readbyqxmd.com/read/29309643/androgen-receptor-splice-variants-bind-to-constitutively-open-chromatin-and-promote-abiraterone-resistant-growth-of-prostate-cancer
#10
Yundong He, Ji Lu, Zhenqing Ye, Siyuan Hao, Liewei Wang, Manish Kohli, Donald J Tindall, Benyi Li, Runzhi Zhu, Liguo Wang, Haojie Huang
Androgen receptor (AR) splice variants (ARVs) are implicated in development of castration-resistant prostate cancer (CRPC). Upregulation of ARVs often correlates with persistent AR activity after androgen deprivation therapy (ADT). However, the genomic and epigenomic characteristics of ARV-dependent cistrome and the disease relevance of ARV-mediated transcriptome remain elusive. Through integrated chromatin immunoprecipitation coupled sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, we identified ARV-preferential-binding sites (ARV-PBS) and a set of genes preferentially transactivated by ARVs in CRPC cells...
January 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29306514/intermediate-endpoints-after-postprostatectomy-radiotherapy-5-year-distant-metastasis-to-predict-overall-survival
#11
William C Jackson, Krithika Suresh, Vasu Tumati, Steven G Allen, Robert T Dess, Simpa S Salami, Arvin George, Samuel D Kaffenberger, David C Miller, Jason W D Hearn, Shruti Jolly, Rohit Mehra, Brent K Hollenbeck, Ganesh S Palapattu, Matthew Schipper, Felix Y Feng, Todd M Morgan, Neil B Desai, Daniel E Spratt
BACKGROUND: Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design. OBJECTIVE: To identify a potential ICE for men receiving PORT. DESIGN, SETTING, AND PARTICIPANTS: We performed an institutional review board-approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013...
January 3, 2018: European Urology
https://www.readbyqxmd.com/read/29302046/p53-status-in-the-primary-tumor-predicts-efficacy-of-subsequent-abiraterone-and-enzalutamide-in-castration-resistant-prostate-cancer
#12
Benjamin L Maughan, Liana B Guedes, Kenneth Boucher, Gaurav Rajoria, Zach Liu, Szczepan Klimek, Roberto Zoino, Emmanuel S Antonarakis, Tamara L Lotan
BACKGROUND: We tested whether tissue-based analysis of p53 and PTEN genomic status in primary tumors is predictive for subsequent sensitivity to abiraterone and enzalutamide in castration-resistant prostate cancer (CRPC). METHODS: We performed a retrospective analysis of 309 consecutive patients with CRPC treated with abiraterone or enzalutamide. Of these, 101 men (33%) had available primary tumor tissue for analysis. We screened for deleterious TP53 missense mutations and PTEN deletions using genetically validated immunohistochemical assays for nuclear accumulation of p53 protein and PTEN protein loss, with sequencing confirmation of TP53 mutations in a subset...
January 4, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29301749/in-situ-detection-and-quantification-of-ar-v7-ar-fl-psa-and-kras-point-mutations-in-circulating-tumor-cells
#13
Amin El-Heliebi, Claudia Hille, Navya Laxman, Jessica Svedlund, Christoph Haudum, Erkan Ercan, Thomas Kroneis, Shukun Chen, Maria Smolle, Christopher Rossmann, Tomasz Krzywkowski, Annika Ahlford, Evangelia Darai, Gunhild von Amsberg, Winfried Alsdorf, Frank König, Matthias Löhr, Inge de Kruijff, Sabine Riethdorf, Tobias M Gorges, Klaus Pantel, Thomas Bauernhofer, Mats Nilsson, Peter Sedlmayr
BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs...
January 4, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29299751/risk-factors-for-unplanned-discontinuation-of-scheduled-treatment-in-elderly-patients-with-castration-resistant-prostate-cancer-results-of-the-ibutu-study
#14
Friedemann Honecker, Ulrich Wedding, Gerd Kallischnigg, Axel Schroeder, Jörg Klier, Thomas Frangenheim, Lothar Weißbach
PURPOSE: To gain knowledge about the factors associated with discontinuation of scheduled treatment in elderly men with castration-resistant prostate cancer (CRPC). METHODS: Patients ≥ 70 years with CRPC starting a new line of treatment were included in a prospective cohort study. A geriatric assessment (CGA) was performed at baseline, including comorbidity, mobility, functional/mental/nutritional status, as well as depression. Furthermore, pain intensity, quality of life, ECOG-performance status, and physicians' and patients' perception of health were documented...
January 4, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29298991/current-approaches-to-incorporation-of-radium-223-in-clinical-practice
#15
REVIEW
Chris Parker, Axel Heidenreich, Sten Nilsson, Neal Shore
BACKGROUND: Treatment options for metastatic castration-resistant prostate cancer (mCRPC) have expanded in recent years and include cytotoxic agents (e.g., docetaxel and cabazitaxel), immunotherapy (e.g., sipuleucel-T), oral hormonal therapies targeting the androgen receptor axis (e.g., enzalutamide and abiraterone), and targeted alpha therapy (e.g., radium-223 dichloride (radium-223)). Although treatment guidelines have been updated to reflect the availability of new agents, it is not easy to apply them in daily clinical practice because recommendations vary depending on patient comorbidities and disease characteristics...
January 3, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29296199/costunolide-enhances-doxorubicin-induced-apoptosis-in-prostate-cancer-cells-via-activated-mitogen-activated-protein-kinases-and-generation-of-reactive-oxygen-species
#16
Jiasheng Chen, Binshen Chen, Zhihui Zou, Wei Li, Yiming Zhang, Jinlin Xie, Chunxiao Liu
The management of castration-resistant prostate cancer (CRPC) is challenging, attributable to a lack of efficacious therapies. Chemotherapy is one of the most important treatments for CRPC. Doxorubicin has been extensively used in many different tumors and is often combined with other drugs to enhance effects and reduce toxicity. Costunolide is a natural sesquiterpene lactone with anti-cancer properties. In this study, we first demonstrated that the combination of costunolide and doxorubicin induced apoptosis significantly more than either drug alone in prostate cancer cell lines...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290796/prlz-increases-prostate-cancer-docetaxel-resistance-by-inhibiting-lkb1-ampk-mediated-autophagy
#17
Jin Zeng, Wei Liu, Yi-Zeng Fan, Da-Lin He, Lei Li
Rationale: Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...
2018: Theranostics
https://www.readbyqxmd.com/read/29288516/il-6-stat3-promotes-prostate-cancer-resistance-to-androgen-deprivation-therapy-via-regulating-pttg1-expression
#18
Shengquan Huang, Qian Liu, Qianjin Liao, Qingjian Wu, Bishao Sun, Zhenxing Yang, Xiaoyan Hu, Mingjia Tan, Longkun Li
Prostate cancer can progress from androgen dependence to androgen deprivation resistance with some unknown mechanisms. The current study aims to explore the possible role of pituitary tumor transforming gene1 (PTTG1) in castration-resistant prostate cancer (CRPC). Initially, we found that PTTG1 expression was significantly increased in androgen-independent prostate cancer cell lines PC3, DU145 and CRPC specimens compared with that in androgen-dependent prostate cancer cell line LNCaP and initial prostate cancer specimens...
December 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/29285670/a-3-variable-prognostic-score-3-ps-for-overall-survival-prediction-in-metastatic-castration-resistant-prostate-cancer-treated-with-223radium-dichloride
#19
Viviana Frantellizzi, Alessio Farcomeni, Giulia Anna Follacchio, Massimiliano Pacilio, Rosanna Pellegrini, Roberto Pani, Giuseppe De Vincentis
OBJECTIVE: In mCRPC patients treated with 223Ra, a major issue is the validation of reliable prognostic and predictive biomarkers to maximize clinical benefit and minimize toxicities and costs. Bearing in mind how changes in tALP did not meet statistical requirements as surrogate marker for survival, aim of this single-center retrospective study was to characterize the prognostic and predictive role of baseline clinical variables associated with overall survival in patients receiving 223Ra treatment...
December 28, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/29285263/predicting-castration-resistant-prostate-cancer-after-combined-androgen-blockade
#20
Miao He, Haina Liu, Jingyi Cao, Qian Wang, Haiting Xu, Yufeng Wang
This study analyzed 99Tcm-MDP bone scans and investigated factors influencing early-stage castration resistance in prostate cancer (CRPC) patients with bone metastasis. We retrospectively analyzed clinical data from 92 patients with bone metastatic prostate cancer treated with maximal androgen blockade. Patients were imaged with 99Tcm-MDP bone scan to detect metastases, and prostate specific antigen (PSA) values were measured regularly. Before treatment, 464 total bone metastases were detected in the 92 patients, with pelvic bone metastases accounting for about 30...
December 1, 2017: Oncotarget
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