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https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#1
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29666302/targeting-galectin-1-impairs-castration-resistant-prostate-cancer-progression-and-invasion
#2
Tsung-Chieh Shih, Ruiwu Liu, Chun-Te Wu, Xiaocen Li, Wenwu Xiao, Xiaojun Deng, Zsofia Kiss, Ting Wang, Xiaojia Chen, Randy P Carney, Hsing-Jien Kung, Yong Duan, Paramita M Ghosh, Kit S Lam
PURPOSE: The majority of prostate cancer (PCa) patients who are treated with androgen deprivation therapy (ADT) will eventually develop fatal metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no effective durable therapies for patients with mCRPC. High expression of Galectin-1 (Gal-1) is associated with PCa progression and poor clinical outcome. The role of Gal-1 in tumor progression are largely unknown. Here we characterized Gal-1 functions and evaluated the therapeutic effects of a newly developed Gal-1inhibitor, LLS30, in mCRPC...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29656854/radical-prostatectomy-in-metastatic-castration-resistant-prostate-cancer-feasibility-safety-and-quality-of-life-outcomes
#3
Chad A Reichard, Justin R Gregg, Mary F Achim, Ana M Aparicio, Curtis A Pettaway, Louis L Pisters, John F Ward, John W Davis, Brian F Chapin
Ongoing prospective studies are evaluating treatment of the primary tumor in men with de novo metastatic prostate cancer (PCa). One potential benefit is prevention of morbidity from local progression. Thus, local therapy may be best applied selectively to men with local progression once resistance to first-line therapies has occurred. Here, we gather support for the hypothesis that radical prostatectomy (RP) is safe and preserves quality of life (QOL) when applied in men with metastatic castration-resistant PCa (mCRPC)...
April 12, 2018: European Urology
https://www.readbyqxmd.com/read/29651569/external-radiation-exposure-excretion-and-effective-half-life-in-177-lu-psma-targeted-therapies
#4
J Kurth, B J Krause, S M Schwarzenböck, L Stegger, M Schäfers, K Rahbar
BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted therapy with 177 Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified. RESULTS: In total, 50 patients with mCRPC and treated with 177 Lu-PSMA-617 (mean administered activity 6...
April 12, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/29626121/reproducibility-and-repeatability-of-semi-quantitative-18-f-fluorodihydrotestosterone-fdht-uptake-metrics-in-castration-resistant-prostate-cancer-metastases-a-prospective-multi-center-study
#5
Hebert Alberto Vargas, Gem M Kramer, Andrew M Scott, Andrew Weickhardt, Andreas A Meier, Nicole Parada, Bradley J Beattie, John L Humm, Kevin D Staton, Pat B Zanzonico, Serge K Lyashchenko, Jason S Lewis, Maqsood Yaqub, Ramon E Sosa, Alfons J van den Eertwegh, Ian D Davis, Uwe Ackermann, Kunthi Pathmaraj, Robert C Schuit, Albert D Windhorst, Sue Chua, Wolfgang A Weber, Steven M Larson, Howard I Scher, Adriaan A Lammertsma, Otto Hoekstra, Michael J Morris
18 F-fluorodihydrotestosterone (18 F-FDHT) is a radiolabeled analogue of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: We conducted a prospective multi-institutional study of mCRPC patients undergoing two (test/re-test)18 F-FDHT PET/CT scans on two consecutive days...
April 6, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29588330/onc201-targets-ar-and-ar-v7-signaling-reduces-psa-and-synergizes-with-everolimus-in-prostate-cancer
#6
Avital Lev, Amriti R Lulla, Brian C Ross, Marie D Ralff, Petr B Makhov, David T Dicker, Wafik S El-Deiry
Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target...
March 27, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29577933/comprehensive-evaluation-of-pd-l1-expression-in-primary-and-metastatic-prostate-cancer
#7
Michael C Haffner, Gunes Guner, Diana Taheri, George J Netto, Doreen N Palsgrove, Qizhi Zheng, Liana Benevides Guedes, Kunhwa Kim, Harrison Tsai, David M Esopi, Tamara Lotan, Rajni Sharma, Alan K Meeker, Arul M Chinnaiyan, William G Nelson, Srinivasan Yegnasubramanian, Jun Luo, Rohit Mehra, Emmanuel S Antonarakis, Charles G Drake, Angelo M De Marzo
Antibodies targeting the PD-1/PD-L1 interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1 specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases...
March 22, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29574703/genomic-alterations-in-plasma-dna-from-patients-with-metastasized-prostate-cancer-receiving-abiraterone-or-enzalutamide
#8
Jelena Belic, Ricarda Graf, Thomas Bauernhofer, Yauheniya Cherkas, Peter Ulz, Julie Waldispuehl-Geigl, Samantha Perakis, Michael Gormley, Jaymala Patel, Weimin Li, Jochen B Geigl, Denis Smirnov, Ellen Heitzer, Mitchell Gross, Michael R Speicher
In patients with metastatic castrate resistant prostate cancer (mCRPC), circulating tumor DNA (ctDNA) analysis offers novel opportunities for the development of non-invasive biomarkers informative of treatment response with novel agents targeting the androgen-receptor (AR) pathway, such as abiraterone or enzalutamide. However, the relationship between ctDNA abundance, detectable somatic genomic alterations and clinical progression of mCRPC remains unexplored. Our study aimed to investigate changes in plasma DNA during disease progression and their associations with clinical variables in mCRPC patients...
March 25, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29565650/recent-advances-in-theranostics-and-challenges-for-the-future
#9
J Harvey Turner
Theranostic nuclear oncology is on the cusp of adoption into routine clinical management of neuroendocrine tumours (NETs) following publication of the Phase 3 randomized controlled trial, NETTER-1. For the first time, level 1b evidence of efficacy and safety of 68-gallium/177 lutetium-DOTA-octreotatepeptide receptor radionuclide therapy (PRRT), of midgut NETs was established. Multicentre Phase 2 studies of 68-gallium/177 lutetium-PSMA theranostic approaches to management of end-stage metastatic castrate-resistant prostate cancer (mCRPC), are also very encouraging...
March 22, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29562686/profiling-prostate-cancer-therapeutic-resistance
#10
REVIEW
Cameron A Wade, Natasha Kyprianou
The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis...
March 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29556815/optimizing-the-treatment-of-metastatic-castration-resistant-prostate-cancer-a-latin-america-perspective
#11
REVIEW
Juan Pablo Sade, Carlos Alberto Vargas Báez, Martin Greco, Carlos Humberto Martínez, Miguel Ángel Álvarez Avitia, Carlos Palazzo, Narciso Hernández Toriz, Patricia Isabel Bernal Trujillo, Diogo Assed Bastos, Fabio Augusto Schutz, Santiago Bella, Lucas Nogueira, Neal D Shore
Prostate cancer is a significant burden and cause of mortality in Latin America. This article reviews the treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) and provides consensus recommendations to assist Latin American prostate cancer specialists with clinical decision making. A multidisciplinary expert panel from Latin America reviewed the available data and their individual experience to develop clinical consensus opinions for the use of life-prolonging agents in mCRPC, with consideration given to factors influencing patient selection and treatment monitoring...
March 19, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29556486/differences-in-clinical-outcome-between-docetaxel-and-abiraterone-acetate-as-the-first-line-treatment-in-chemo-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer-patients-with-or-without-the-ineligible-clinical-factors-of-the-cou-aa-302-study
#12
Darren M C Poon, Kuen Chan, Siu H Lee, Tim W Chan, Henry Sze, Eric K C Lee, Daisy Lam, Michelle F T Chan
Background: This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2). Materials and methods: The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed...
March 2018: Prostate International
https://www.readbyqxmd.com/read/29555412/the-resounding-effect-of-dna-repair-deficiency-in-prostate-cancer
#13
REVIEW
Heather H Cheng
An estimated one-fifth or more of metastatic castration-resistant prostate cancer (mCRPC) harbor defects in genes involved in DNA repair pathway (e.g., BRCA2, BRCA1, and others). Early evidence suggests these alterations may be predictive of therapeutic response to PARP inhibitors and platinum chemotherapy, thought to reflect principles of synthetic lethality and are currently being investigated in an increasing number of prospective clinical trials. Other studies have examined these alterations as prognostic biomarkers and in association with response to currently available treatments...
March 16, 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29553053/bone-targeted-therapies-to-reduce-skeletal-morbidity-in-prostate-cancer
#14
Tanya B Dorff, Neeraj Agarwal
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA...
March 16, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29550200/results-of-the-flac-european-database-of-metastatic-castration-resistant-prostate-cancer-patients-treated-with-docetaxel-cabazitaxel-and-androgen-receptor-targeted-agents
#15
Antoine Angelergues, Eleni Efstathiou, Revekka Gyftaki, Piotr Jan Wysocki, Nuria Lainez, Iria Gonzalez, Daniel E Castellano, Mustafa Ozguroglu, Iciar Garcia Carbonero, Aude Flechon, Pablo Borrega, Aline Guillot, Begona Campos Balea, Sylvestre Le Moulec, Emilio Esteban, Javier Munarriz, Gustavo Rubio, Alison J Birtle, Nicolas Delanoy, Joaquim Bellmunt, Stéphane Oudard
BACKGROUND: Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor-targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC)...
February 23, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29542849/expression-of-tumour-progression-associated-genes-in-circulating-tumour-cells-of-patients-at-different-stages-of-prostate-cancer
#16
Giorgio I Russo, Simone Bier, Jörg Hennenlotter, Gunthild Beger, Lucretia Pavlenco, Jens van de Flierdt, Siegfried Hauch, Moritz Maas, Simon Walz, Steffen Rausch, Jens Bedke, Giuseppe Morgia, Arnulf Stenzl, Tilman Todenhöfer
OBJECTIVE: To evaluate the presence of circulating tumour cells (CTCs) at different stages of prostate cancer using the AdnaTest® ProstateCancerDetect kit (Qiagen). Moreover, we aimed to assess the expression of transcripts that are specific for cancer stem cells (AdnaTest StemCell) and epithelial-mesenchymal transition (EMT) in CTCs (AdnaTest EMT), as well as additional genes that are known to promote prostate cancer progression. PATIENTS AND METHODS: In this prospective study, we included 81 patients who underwent treatment for prostate cancer between 07/2014 and 02/2015, including: Group A, 18 patients (22...
March 15, 2018: BJU International
https://www.readbyqxmd.com/read/29540470/sprouty2-loss-induced-il6-drives-castration-resistant-prostate-cancer-through-scavenger-receptor-b1
#17
Rachana Patel, Janis Fleming, Ernest Mui, Carolyn Loveridge, Peter Repiscak, Arnaud Blomme, Victoria Harle, Mark Salji, Imran Ahmad, Katy Teo, Freddie C Hamdy, Ann Hedley, Niels van den Broek, Gillian Mackay, Joanne Edwards, Owen J Sansom, Hing Y Leung
Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self-sufficient form of CRPC Mechanistically, HER2-IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1-mediated cholesterol uptake in SPRY2-deficient tumours...
March 14, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29534939/phase-i-trial-of-the-combination-of-docetaxel-prednisone-and-pasireotide-in-metastatic-castrate-resistant-prostate-cancer
#18
Manish K Thakur, Lance Heilbrun, Kimberlee Dobson, Julie Boerner, Karri Stark, Jing Li, Daryn Smith, Elisabeth Heath, Joseph Fontana, Ulka Vaishampayan
BACKGROUND: Pasireotide (SOM230; Novartis Inc, Basel, Switzerland) is a multitargeted somatostatin receptor analogue likely to treat the neuroendocrine, and docetaxel resistant components within metastatic castrate-resistant prostate cancer (mCRPC). This phase I trial tested the combination of pasireotide, docetaxel, and prednisone in pretreated mCRPC. PATIENTS AND METHODS: Chemotherapy naive mCRPC patients received docetaxel 75 mg/m2 intravenously every 21 days and pasireotide intramuscularly every 28 days at escalating dose levels of 40, 60, and 80 mg...
February 13, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29534736/prime-boost-vaccination-targeting-prostatic-acid-phosphatase-pap-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc-using-sipuleucel-t-and-a-dna-vaccine
#19
Ellen Wargowski, Laura E Johnson, Jens C Eickhoff, Lauren Delmastro, Mary Jane Staab, Glenn Liu, Douglas G McNeel
BACKGROUND: Prostatic acid phosphatase (PAP) is a prostate tumor antigen, and the target of the only FDA-approved anti-tumor vaccine, sipuleucel-T. We have previously reported in two clinical trials that a DNA vaccine encoding PAP (pTVG-HP) could elicit PAP-specific, Th1-biased T cells in patients with PSA-recurrent prostate cancer. In the current pilot trial we sought to evaluate whether this vaccine could augment PAP-specific immunity when used as a booster to immunization with sipuleucel-T in patients with metastatic, castration-resistant prostate cancer (mCRPC)...
March 13, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29533860/quantitation-of-the-anticancer-drug-abiraterone-and-its-metabolite-%C3%AE-4-abiraterone-in-human-plasma-using-high-resolution-mass-spectrometry
#20
Atul Bhatnagar, Matthew J McKay, Megan Crumbaker, Ketan Ahire, Peter Karuso, Howard Gurney, Mark P Molloy
Abiraterone acetate is administered as a prodrug to patients with metastatic, castration-resistant prostate cancer (mCRPC) and is readily metabolized into the potent 17a-hydroxylase/17,20-lyase (CYP17) enzyme inhibitor and androgen receptor inhibitor abiraterone and Δ(4)-abiraterone (D4A), respectively. To investigate pharmacokinetic variability in abiraterone acetate metabolism we developed highly sensitive liquid chromatography/mass spectrometry (LC/MS) assays for the simultaneous quantitation of abiraterone and D4A in human plasma using high-resolution mass spectrometry (HRMS) on an Orbitrap mass spectrometer...
March 6, 2018: Journal of Pharmaceutical and Biomedical Analysis
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