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Metastatic prostatic cancer clinical treatment

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https://www.readbyqxmd.com/read/29450905/a-tramp-derived-orthotopic-prostate-syngeneic-tops-cancer-model-for-investigating-anti-tumor-treatments
#1
Justin Lardizabal, Jun Ding, Zahid Delwar, Paul S Rennie, William Jia
BACKGROUND: Patients with advanced prostate cancer have limited curative options, therefore new treatments are needed. Mouse models play a pivotal role in the discovery and development of new treatments. In the present study, a TRAMP-derived Orthotopic Prostate Syngeneic (TOPS) mouse model was developed and found to provide a consistent means of monitoring tumor and metastatic responses to novel treatments. METHODS: The mouse TOPS model was generated using luciferase transduced TRAMP-C2 prostate cancer cells that were orthotopically injected into Bl6 mice by ultrasound guidance...
February 16, 2018: Prostate
https://www.readbyqxmd.com/read/29446748/anti-oxidants-as-chemopreventive-agents-in-prostate-cancer-a-gap-between-preclinical-and-clinical-studies
#2
Monireh Mohsenzadegan, Farhad Seif, Mohammad Morad Farajollahi, Majid Khoshmirsafa
BACKGROUND: Tumor cells may be expressed as a result of oxidative stress. The extent of oxidative stress correlates with aggressive and metastatic potency of cancer. OBJECTIVE: One simple way to control prostate cancer is through chemoprevention which refers to the administration of natural or synthetic agents to block, reverse, or delay the process of carcinogenesis. The most chemopreventive agents are antioxidants in the nature. METHODS: In this review, we summarized the effects of dietary antioxidants with a focus on their molecular mechanisms and possible roles in the treatment of prostate cancer cells...
February 13, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29439820/germline-dna-repair-gene-mutations-and-outcomes-in-men-with-metastatic-castration-resistant-prostate-cancer-receiving-first-line-abiraterone-and-enzalutamide
#3
Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Chao Liang, Hao Wang, Yan Chen, John L Silberstein, Danilo Piana, Zhao Lai, Yidong Chen, William B Isaacs, Jun Luo
BACKGROUND: Inherited DNA-repair gene mutations are more prevalent in men with advanced prostate cancer than previously thought, but their clinical implications are not fully understood. OBJECTIVE: To investigate the clinical significance of germline DNA-repair gene alterations in men with metastatic castration-resistant prostate cancer (mCRPC) receiving next-generation hormonal therapy (NHT), with a particular emphasis on BRCA/ATM mutations. DESIGN, SETTING, AND PARTICIPANTS: We interrogated 50 genes for pathogenic or likely pathogenic germline mutations using leukocyte DNA from 172 mCRPC patients beginning treatment with first-line NHT with abiraterone or enzalutamide...
February 10, 2018: European Urology
https://www.readbyqxmd.com/read/29434673/practical-differences-between-luteinizing-hormone-releasing-hormone-agonists-in-prostate-cancer-perspectives-across-the-spectrum-of-care
#4
REVIEW
Davide Meani, Mladen Solarić, Harri Visapää, Rose-Marie Rosén, Robert Janknegt, Majana Soče
Background: Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonists is well established for the treatment of men with metastatic prostate cancer. As clear differences in efficacy, safety, or tolerability between the available LHRH agonists are lacking, the healthcare management team needs to look to practical differences between the formulations when selecting therapy for their patients. Moreover, as the economic burden of prostate cancer rises alongside earlier diagnosis and improved survival, the possibility for cost savings by using products with specific features is growing in importance...
February 2018: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/29431540/pharmacokinetic-pharmacodynamic-drug-evaluation-of-enzalutamide-for-treating-prostate-cancer
#5
Jeong Hee Hong
Enzalutamide is the first approved second-generation androgen receptor (AR) antagonist in the treatment of metastatic castration-resistant prostate cancer (mCRPC) with or without docetaxel-based chemotherapy. Over the past 5 years, a number of attempts were made to determine the efficacy of enzalutamide in the different clinical settings. Areas covered: A literature search was performed at the PubMed, Embase, and Web of Science database to collect the most relevant and impactful studies, including basic science investigations, clinical trials, and reviews...
February 12, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29431193/circulating-tumor-cells-and-survival-in-abiraterone-and-enzalutamide-treated-patients-with-castration-resistant-prostate-cancer
#6
Bram De Laere, Steffi Oeyen, Peter Van Oyen, Christophe Ghysel, Jozef Ampe, Piet Ost, Wim Demey, Lucien Hoekx, Dirk Schrijvers, Barbara Brouwers, Willem Lybaert, Els Everaert, Piet Van Kerckhove, Daan De Maeseneer, Michiel Strijbos, Alain Bols, Karen Fransis, Nick Beije, Inge de Kruijff, Valerie van Dam, Anja Brouwer, Pieter-Jan van Dam, Gert Van den Eynden, Annemie Rutten, Stefan Sleijfer, Jean Vandebroek, Steven Van Laere, Luc Dirix
BACKGROUND: The outcome to treatment administered to patients with metastatic castration-resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making. OBJECTIVE: To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second-line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies...
February 12, 2018: Prostate
https://www.readbyqxmd.com/read/29423595/alpha-emitters-and-targeted-alpha-therapy-in-oncology-from-basic-science-to-clinical-investigations
#7
Mehran Makvandi, Edouard Dupis, Jonathan W Engle, F Meiring Nortier, Michael E Fassbender, Sam Simon, Eva R Birnbaum, Robert W Atcher, Kevin D John, Olivier Rixe, Jeffrey P Norenberg
Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting...
February 8, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29422356/will-68ga-psma-radioligands-be-the-only-choice-for-nuclear-medicine-in-prostate-cancer-in-the-near-future-a-clinical-update
#8
V Cuccurullo, G D di Stasio, L Evangelista, A Ciarmiello, L Mansi
Prostate Cancer (PCa) represents the most common malignant tumor in men but according to the European Association of Urology (EAU) guidelines, a mass screening for PCa diagnosis should not be performed due to over-diagnosis and over-treatment related problems. An early clinical diagnosis is possible, mainly based on digital rectal examination and Prostatic Specific Agent (PSA) testing. However, the only mandatory test to define the presence of PCa is ultrasound guided-biopsy, obtained on multiple samples, which has also a high prognostic value...
February 5, 2018: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/29421982/immune-based-therapies-for-metastatic-prostate-cancer-an-update
#9
Md Kamal Hossain, Kamrun Nahar, Osaana Donkor, Vasso Apostolopoulos
Prostate cancer (PC) is a common malignancy among elderly males and is noncurable once it becomes metastatic. In recent years, a number of antigen-delivery systems have emerged as viable and promising immunotherapeutic agents against PC. The approval of sipuleucel-T by the US FDA for the treatment of males with asymptomatic or minimally symptomatic castrate resistant PC was a landmark in cancer immunotherapy, making this the first approved immunotherapeutic. A number of vaccines are under clinical investigation, each having its own set of advantages and disadvantages...
February 1, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29419723/development-and-validation-of-a-bioanalytical-method-to-quantitate-enzalutamide-and-its-active-metabolite-n-desmethylenzalutamide-in-human-plasma-application-to-clinical-management-of-metastatic-castration-resistant-prostate-cancer-patients
#10
Guillemette E Benoist, Eric van der Meulen, Inge M van Oort, Jan Hendrik Beumer, Diederik M Somford, Jack A Schalken, David M Burger, Nielka P van Erp
BACKGROUND: Enzalutamide is a potent androgen-signaling receptor inhibitor and is licensed for the treatment of metastatic castration-resistant prostate cancer. N-desmethylenzalutamide is the active metabolite of enzalutamide. A method to quantitate enzalutamide and its active metabolite was developed and validated according to the European Medicine Agency (EMA) guidelines. METHODS: Enzalutamide and N-desmethylenzalutamide were extracted by protein precipitation, separated on a C18 column with gradient elution and analyzed with tandem quadruple mass spectrometry in positive ion mode...
February 5, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29406415/magnetic-resonance-imaging-guided-high-intensity-focused-ultrasound-applications-in-pediatrics-early-experience-at-children-s-national-medical-center
#11
Karun V Sharma, Pavel S Yarmolenko, Avinash Eranki, Ari Partanen, Haydar Celik, AeRang Kim, Matthew Oetgen, Peter C W Kim
Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) is a novel technology that integrates magnetic resonance imaging with therapeutic ultrasound. This unique approach provides a completely noninvasive method for precise thermal ablation of targeted tissues with real-time imaging feedback. Over the past 2 decades, MR-HIFU has shown clinical success in several adult applications ranging from treatment of painful bone metastases to uterine fibroids to prostate cancer and essential tremor...
February 2018: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/29404276/estrogens-and-their-receptors-in-prostate-cancer-therapeutic-implications
#12
REVIEW
Erika Di Zazzo, Giovanni Galasso, Pia Giovannelli, Marzia Di Donato, Gabriella Castoria
A major challenge in clinical management of prostate cancer (PC) is to limit tumor growth and prevent metastatic spreading. Considerable efforts have been made to discover new compounds for PC therapy and recent years have seen promising progress in this field. Pharmacological approaches have been designed to achieve benefits in PC treatment and avoid the negative side effects resulting from administration of antagonists or agonists or new drugs. Nonetheless, the currently available therapies frequently induce resistance and PC progresses toward castration-resistant forms that can be caused by the androgen receptor reactivation and/or mutations, or derangement of signaling pathways...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29399158/microrna-1-inhibits-tumorigenicity-of-esophageal-squamous-cell-carcinoma-and-enhances-sensitivity-to-gefitinib
#13
Qianqian Yu, Yiqian Liu, Chengcai Wen, Yongzhao Zhao, Shidai Jin, Youfang Hu, Feng Wang, Liang Chen, Bin Zhang, Wei Wang, Quan Zhu, Renhua Guo
Dysregulation of microRNAs in various types of human cancer promote or suppress oncogenesis. MicroRNA (miR)-1 was previously revealed to function as a tumor suppressor in prostate cancer cells, and its expression was associated with reduced metastatic potential in lung cancer. The present study investigated the role of miR-1 and its association with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) in the pathophysiology of esophageal squamous cell carcinoma (ESCC), and analyzed the effects of miR-1 inhibitor or mimics on sensitivity to epidermal growth factor receptor-tyrosine kinase inhibitors, the alterations of cell cycle distribution and apoptosis in ESCC cells...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29398263/expression-of-androgen-receptor-splice-variant-7-or-9-in-whole-blood-does-not-predict-response-to-androgen-axis-targeting-agents-in-metastatic-castration-resistant-prostate-cancer
#14
Sarah Q To, Edmond M Kwan, Heidi C Fettke, Andrew Mant, Maria M Docanto, Luciano Martelotto, Patricia Bukczynska, Nicole Ng, Lisa-Jane K Graham, Phillip Parente, Carmel Pezaro, Kate Mahon, Lisa Horvath, Tilman Todenhöfer, Arun A Azad
In 2014, a landmark study was published demonstrating that the expression of androgen receptor splice variant (AR-V) 7 was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumour cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR-Vs and treatment response...
February 2, 2018: European Urology
https://www.readbyqxmd.com/read/29396636/imaging-%C3%AE-v%C3%AE-3-integrin-expression-in-skeletal-metastases-with-99mtc-maraciclatide-single-photon-emission-computed-tomography-detection-and-therapy-response-assessment
#15
Gary J R Cook, Gurdip K Azad, Benjamin P Taylor, Eugene Lee, Matthew S Morrison, Simon Hughes, Stephen Morris, Sarah Rudman, Simon Chowdhury, Vicky Goh
PURPOSE: Osteoclast activity is an important factor in the pathogenesis of skeletal metastases and is a potential therapeutic target. This study aimed to determine if selective uptake of 99mTc-maraciclatide, a radiopharmaceutical targeting αvβ3 integrin, occurs in prostate cancer (PCa) bone metastases and to observe the changes following systemic therapy. METHODS: The study group comprised 17 men with bone-predominant metastatic PCa who underwent whole-body planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging with 99mTc-maraciclatide before (n = 17) and 12 weeks after (n = 11) starting treatment with abiraterone...
February 2, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29395951/epigenetic-reprogramming-a-key-mechanism-driving-therapeutic-resistance
#16
REVIEW
Anjali V Sheahan, Leigh Ellis
Prostate cancer initiation, development and progression is driven by androgen receptor (AR) signaling. Androgen deprivation therapy is the primary treatment for patients that present with locally advanced or metastatic disease. However, androgen deprivation therapy is not curative, and patients will progress to castrate-resistant disease (CRPC). Although most patient's progress to CRPC via restoration of AR signaling (CRPC-Ad), approximately a quarter of patients will progress via mechanisms independent of AR signaling...
January 26, 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29394925/nc886-is-epigenetically-repressed-in-prostate-cancer-and-acts-as-a-tumor-suppressor-through-the-inhibition-of-cell-growth
#17
Rafael Sebastián Fort, Cecilia Mathó, Murilo Vieira Geraldo, María Carolina Ottati, Alex Shimura Yamashita, Kelly Cristina Saito, Katia Ramos Moreira Leite, Manuel Méndez, Noemí Maedo, Laura Méndez, Beatriz Garat, Edna Teruko Kimura, José Roberto Sotelo-Silveira, María Ana Duhagon
BACKGROUND: Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer...
February 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29388415/innovations-in-imaging-modalities-for-recurrent-and-metastatic-prostate-cancer-a-systematic-review
#18
Simone Albisinni, Fouad Aoun, Quentin Marcelis, Claude Jungels, Walid Al Hajj Obeid, Marc Zanaty, Andrea Tubaro, Thierry Roumeguere, Cosimo DE Nunzio
INTRODUCTION: The last decade has witnessed tremendous changes in the management of advanced and metastatic castration resistant prostate cancer (mCRPC). In the current systematic review, we analyze novel imaging techniques in the setting of recurrent and metastatic PCa, exploring available data and highlighting future exams which could enter clinical practice in the upcoming years. EVIDENCE ACQUISITION: The National Library of Medicine Database was searched for relevant articles published between January 2012 and August 2017...
January 31, 2018: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/29387407/effect-on-prostate-volume-following-neoadjuvant-treatment-with-an-androgen-receptor-inhibitor-monotherapy-versus-castration-plus-an-androgen-receptor-inhibitor-in-prostate-cancer-patients-intended-for-curative-radiation-therapy-a-randomised-study
#19
Khairul Majumder, Yvonne Brandberg, Hemming Johansson, Enrique Castellanos, Anders Ullén, Bo Lennernäs, Sten Nilsson
To avoid pubic arch interference, prostate cancer patients are treated with neoadjuvant androgen deprivation therapy (ADT) to achieve prostate volume (PV) reduction prior to radiation treatment. The aim of the present randomised study was to compare the effects on PV of two regimens of ADT, an androgen receptor inhibitor monotherapy vs. castration plus an androgen receptor inhibitor. Consecutive patients with non-metastatic prostate cancer were included in a randomised neoadjuvant study, comparing an androgen receptor inhibitor monotherapy vs...
January 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29384591/a-clinically-relevant-decrease-in-abiraterone-exposure-associated-with-carbamazepine-use-in-a-patient-with-castration-resistant-metastatic-prostate-cancer
#20
G E Benoist, M J van der Doelen, R Ter Heine, N P van Erp, N Mehra
ADVERSE EVENT: Decreased abiraterone exposure after introducing carbamazepine DRUGS IMPLICATED: Abiraterone acetate and carbamazepine THE PATIENT: A 65-year-old man with metastatic castration resistant prostate cancer, was treated with abiraterone acetate and prednisolone, and received concomitant carbamazepine for treatment of facial neuropathy EVIDENCE THAT LINKS THE DRUG TO THE EVENT: The interaction was confirmed by a decrease in abiraterone exposure > 2-fold (area-under-the-curve and trough levels)...
January 31, 2018: British Journal of Clinical Pharmacology
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