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Metastatic castrate resistant prostate cancer

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https://www.readbyqxmd.com/read/28430640/epithelial-mesenchymal-transition-in-prostate-cancer-an-overview
#1
REVIEW
Micaela Montanari, Sabrina Rossetti, Carla Cavaliere, Carmine D'Aniello, Maria Gabriella Malzone, Daniela Vanacore, Rossella Di Franco, Elvira La Mantia, Gelsomina Iovane, Raffaele Piscitelli, Raffaele Muscariello, Massimiliano Berretta, Sisto Perdonà, Paolo Muto, Gerardo Botti, Attilio Antonio Montano Bianchi, Bianca Maria Veneziani, Gaetano Facchini
Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer.Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428880/long-term-complete-remission-with-ipilimumab-in-metastatic-castrate-resistant-prostate-cancer-case-report-of-two-patients
#2
Luc Cabel, Elika Loir, Gwenaelle Gravis, Pernelle Lavaud, Christophe Massard, Laurence Albiges, Giulia Baciarello, Yohann Loriot, Karim Fizazi
BACKGROUND: Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28427521/management-of-metastatic-castration-resistant-prostate-cancer-a-focus-on-radium-223-opinions-and-suggestions-from-an-expert-multidisciplinary-panel
#3
REVIEW
Sergio Baldari, Giuseppe Boni, Roberto Bortolus, Orazio Caffo, Giario Conti, Giuseppe De Vincentis, Fabio Monari, Giuseppe Procopio, Daniele Santini, Ettore Seregni, Riccardo Valdagni
Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427519/a-comprehensive-review-of-immunotherapies-in-prostate-cancer
#4
REVIEW
Manuel Caitano Maia, Aaron R Hansen
Prostate cancer is the second most common malignant neoplasm in men worldwide and the fifth cause of cancer-related death. Although multiple new agents have been approved for metastatic castration resistant prostate cancer over the last decade, it is still an incurable disease. New strategies to improve cancer control are needed and agents targeting the immune system have shown encouraging results in many tumor types. Despite being attractive for immunotherapies due to the expression of various tumor associated antigens, the microenvironment in prostate cancer is relatively immunosuppressive and may be responsible for the failures of various agents targeting the immune system in this disease...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#5
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427152/radioligand-therapy-of-metastatic-prostate-cancer-using-177lu-psma-617-after-radiation-exposure-to-223ra-dichloride
#6
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with 177Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with 223Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of 177Lu-PSMA-617 after exposure to more cycles of 223Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with 223Ra...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426121/phase-ii-study-of-cabazitaxel-with-or-without-abiraterone-acetate-and-prednisone-in-patients-with-metastatic-castrate-resistant-prostate-cancer-after-prior-docetaxel-and-abiraterone-acetate
#7
E R Kessler, D Gao, T W Flaig, K Breaker, M Wold, M Wacker, E T Lam
No abstract text is available yet for this article.
March 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28426107/controversies-and-consensus-in-the-innovation-access-for-cancer-therapy-in-the-european-countries-on-the-subject-of-metastatic-prostate-cancer
#8
S Oudard, F Courbon
Innovative cancer therapies and advances in drug development have created new hopes for patients and health providers. The purpose of this article was to evaluate the discrepancies in the assessment of the magnitude of benefit of four new drugs (abiraterone acetate, enzalutamide, cabazitaxel, radium-223 dichloride) for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The comparison was done among three European countries (UK, Germany and France) and Canada, according to the statement of each country and to the European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425029/comparison-of-a-novel-formulation-of-abiraterone-acetate-vs-the-originator-formulation-in-healthy-male-subjects-two-randomized-open-label-crossover-studies
#9
Ronald Goldwater, Azra Hussaini, Bill Bosch, Paul Nemeth
BACKGROUND AND OBJECTIVE: Abiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer. The originator abiraterone acetate (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic variability in abiraterone exposure. Abiraterone acetate fine particle (AAFP) is a proprietary formulation (using SoluMatrix Fine Particle Technology™) designed to increase the oral bioavailability of abiraterone acetate. Here, we report on two phase I studies in healthy male subjects aged 18-50 years...
April 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28423666/negative-lc3b-immunoreactivity-in-cancer-cells-is-an-independent-prognostic-predictor-of-prostate-cancer-specific-death
#10
Ashkan Mortezavi, Souzan Salemi, Niels J Rupp, Jan Hendrik Rüschoff, Thomas Hermanns, Cedric Poyet, Marco Randazzo, Hans-Uwe Simon, Holger Moch, Tullio Sulser, Peter Wild, Daniel Eberli
BACKGROUND: Autophagy is a catabolic cellular process used for degradation of cytoplasmic organelles and preservation of cell viability. In this study we aimed to analyse the level of autophagy markers in benign and malignant prostate tissue and to evaluate the prognostic properties for patients with prostate cancer (PCa). RESULTS: LC3b expression was significantly upregulated in PCa, especially in metastatic and castration-resistant PCa samples compared to benign prostate tissue (p<0...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422308/androgen-receptor-regulated-mirna-193a-3p-targets-ajuba-to-promote-prostate-cancer-cell-migration
#11
Li Jia, Bin Gui, Dali Zheng, Keith F Decker, Ilker Tinay, Mingyue Tan, Xiaowei Wang, Adam S Kibel
Background Dysregulation of microRNA (miRNA) expression is implicated in cancer development and progression by modulating oncogenes or tumor suppressors at the post-transcriptional level. Methods To investigate the role of miRNAs in prostate cancer (PCa) progression, we performed small RNA-sequencing (RNA-seq) analysis in androgen-dependent LNCaP cells and LNCaP-derived castration-resistant prostate cancer (CRPC) C4-2B cells. For functional validation, we specifically investigated miR-193a-3p, which is highly upregulated in C4-2B cells and modulated by the androgen receptor (AR)...
April 19, 2017: Prostate
https://www.readbyqxmd.com/read/28421240/a-randomised-phase-ii-study-of-repeated-rhenium-188-hedp-combined-with-docetaxel-and-prednisone-versus-docetaxel-and-prednisone-alone-in-castration-resistant-prostate-cancer-crpc-metastatic-to-bone-the-taxium-ii-trial
#12
Joyce M van Dodewaard-de Jong, John M H de Klerk, Haiko J Bloemendal, Daniela E Oprea-Lager, Otto S Hoekstra, H Pieter van den Berg, Maartje Los, Aart Beeker, Marianne A Jonker, Joe M O'Sullivan, Henk M W Verheul, Alfons J M van den Eertwegh
BACKGROUND: Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for palliation of metastatic bone pain. We investigated whether the addition of rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in patients with CRPC. METHODS: Patients with progressive CRPC and osteoblastic bone metastases were randomised for first-line docetaxel 75 mg/m(2) 3-weekly plus prednisone with or without 2 injections of rhenium-188-HEDP after the third (40 MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel...
April 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28415742/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#13
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413162/whole-genome-sequence-of-the-metastatic-pc3-and-lncap-human-prostate-cancer-cell-lines
#14
Inge Seim, Penny L Jeffery, Patrick B Thomas, Colleen C Nelson, Lisa K Chopin
The bone metastasis-derived PC3 and the lymph node metastasis-derived LNCaP prostate cancer cell lines are widely studied, having been described in thousands of publications over the last four decades. Here, we report short-read whole-genome sequencing and de novo assembly of PC3 (ATCC CRL-1435) and LNCaP (clone FGC; ATCC CRL-1740) at ~70X coverage. A known homozygous mutation in TP53 and homozygous loss of PTEN were robustly identified in the PC3 cell line, whereas the LNCaP cell line exhibited a larger number of putative inactivating somatic point and indel mutations (and in particular loss of stop codon events)...
April 16, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28411479/aged-patients-with-metastatic-castration-resistant-prostate-cancer-should-we-treat-with-chemotherapy
#15
REVIEW
Miguel Ángel Climent, Ma Dolores Torregrosa, Sergio Vázquez, Regina Gironés, José Angel Arranz
Prostate cancer largely affects aged men and as life expectancy continues to increase, it is likely to be a growing burden requiring an adequate management. Aging is a heterogeneous process, thus, to assess the individual state of health when making decisions is essential. Comprehensive geriatric assessment allows a detailed evaluation of the state of health of a specific subject and can modify the therapeutic decision. It is still not commonly used because it is time consuming. Chemotherapy should be administered equally in aged well-fit patients as in the general population as per the SIOG (International society of geriatric oncology) recommendations for geriatric evaluation and treatment in prostate cancer patients...
April 3, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28410987/alkaline-phosphatase-velocity-predicts-overall-survival-and-bone-metastasis-in-patients-with-castration-resistant-prostate-cancer
#16
Kai H Hammerich, Timothy F Donahue, Inger L Rosner, Jennifer Cullen, Huai-Ching Kuo, Lauren Hurwitz, Yongmei Chen, Melanie Bernstein, Jonathan Coleman, Daniel C Danila, Adam R Metwalli
INTRODUCTION AND OBJECTIVES: Identifying patients with prostate cancer (CaP) who will ultimately develop bone metastasis (BM) or die of disease is essential. Alkaline phosphatase velocity (APV) has been shown to predict overall survival (OS) and bone metastasis-free survival (BMFS) in an earlier study of an equal access military patient cohort of patients with castrate-resistant prostate cancer (CRPC). To confirm these findings, we examined a cohort of patients from a high-volume cancer center to validate a previous observation that faster alkaline phosphatase (AP) kinetics are predictive of OS and BMFS in this second cohort of patients...
April 11, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28408529/targeted-alpha-therapy-of-mcrpc-with-225-actinium-psma-617-dosimetry-estimate-and-empirical-dose-finding
#17
Clemens Kratochwil, Frank Bruchertseifer, Hendrik Rathke, Marcus Bronzel, Christos Apostolidis, Wilko Weichert, Uwe Haberkorn, Frederick Lars Giesel, Alfred Morgenstern
To develop a treatment protocol for (225)Ac-PSMA-617 alpha-radiation therapy in advanced stage, metastatic castration-resistant prostate cancer patients with PSMA-positive tumor phenotype. Methods: A dosimetry estimate was calculated based on time-activity-curves derived from serially performed (177)Lu-PSMA-617 scans extrapolated to the physical half-life of (225)Ac, assuming instant decay of instable daughter nuclides. Salvage therapies empirically conducted with 50kBq/kg (n = 4), 100kBq/kg (n = 4), 150kBq/kg (n = 2), 200kBq/kg (n = 4) (225)Ac-PSMA-617 were evaluated retrospectively regarding toxicity and treatment response...
April 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28408152/cellular-determinants-and-microenvironmental-regulation-of-prostate-cancer-metastasis
#18
REVIEW
Kiera Rycaj, Hangwen Li, Jianjun Zhou, Xin Chen, Dean G Tang
Metastasis causes more than 90% of cancer-related deaths and most prostate cancer (PCa) patients also die from metastasis. The 'metastatic cascade' is a complex biological process that encompasses tumor cell dissociation (from the primary tumor), local invasion, intravasation, transport in circulation, extravasation, colonization, and overt growth in end organs. It has become clear that successful metastasis not only involves many tumor cell-intrinsic properties but also depends on productive interactions between cancer cells and the tumor microenvironment...
April 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28401143/impact-of-abiraterone-acetate-with-and-without-prior-docetaxel-chemotherapy-on-the-survival-of-patients-with-metastatic-castration-resistant-prostate-cancer-a-population-based-study
#19
Joice Rocha, Armen G Aprikian, Marie Vanhuyse, Fabio L Cury, Jason Hu, Noémie Prévost, Alice Dragomir
BACKGROUND: Abiraterone acetate was introduced in Quebec in 2012 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients who had received chemotherapy with docetaxel. This study describes abiraterone use in the early postapproval period and its clinical effectiveness in Quebec, for both patients who had received docetaxel chemotherapy and those who could not receive docetaxel therapy owing to medical reasons. METHODS: A retrospective cohort study was conducted using Quebec public health care administrative databases...
January 2017: CMAJ Open
https://www.readbyqxmd.com/read/28399110/towards-better-dose-individualisation-metabolic-phenotyping-to-predict-cabazitaxel-pharmacokinetics-in-men-with-prostate-cancer
#20
A Janssen, C P M Verkleij, A van der Vlist, R H J Mathijssen, H J Bloemendal, R Ter Heine
BACKGROUND: Cabazitaxel is approved for treatment of castration-resistant metastatic prostate cancer. The current dosing strategy of cabazitaxel is based on body surface area (BSA). Body surface area is known as a poor predictor for total systemic exposure to drugs, since it does not take into account variability in activity of metabolising enzymes, necessary for clearance of drugs. As exposure to cabazitaxel is related to treatment response, it is essential to develop a better individualised dosing strategy...
April 11, 2017: British Journal of Cancer
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