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Novel treatments prostate

Weerachai Jaratlerdsiri, Eva K F Chan, Tingting Gong, Desiree C Petersen, Anton M F Kalsbeek, Philip A Venter, Phillip D Stricker, Ms Riana Bornman, Vanessa M Hayes
African American men are more likely than any other racial group to die from prostate cancer. The contribution of acquired genomic variation to this racial disparity is largely unknown, as genomic from Africa is lacking. Here we performed the first tumor-normal paired deep whole-genome sequencing for Africa. A direct study-matched comparison between African- and European-derived, treatment-naïve, high-risk prostate tumors for 15 cases allowed for further comparative analyses of existing data. Excluding a single hyper-mutated tumor with 55 mutations per megabase, we observed a 1...
September 14, 2018: Cancer Research
Shan Wang, Dede N Ekoue, Ganesh V Raj, Ralf Kittler
The current therapeutic armamentarium for castration-resistant prostate cancer (CRPC) includes second-generation agents such as the Androgen Receptor (AR) inhibitor enzalutamide and the androgen synthesis inhibitor abiraterone acetate, immunotherapies like sipuleucel-T, chemotherapies including docetaxel and cabazitaxel and the radiopharmaceutical radium 223 dichloride. However, relapse of CRPC resistant to these therapeutic modalities occur rapidly. The mechanisms of resistance to these treatments are complex, including specific mutations or alternative splicing of oncogenic proteins...
September 11, 2018: Cancer Letters
Umberto Anceschi, Gabriele Tuderti, Franco Lugnani, Piermario Biava, Gianni Malossini, Lorenzo Luciani, Tommaso Cai, Davide Marsiliani, Alessio Filianoti, Daniele Mattevi, Manuela Costantini, Leonardo Misuraca, Giuseppe Simone
In recent years, several biomarkers alternative to standard prostate specific antigen (PSA) for prostate cancer (PCa) diagnosis have become available. The aim of this systematic review is to assess the current knowledge about alternative serum and urinary biomarkers for the diagnosis of PCa. Material and Methods A research was conducted in Medline, restricted to English language articles published between December 2014 and June 2018 with the aim to update previously published series on PCa biomarkers. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria were used for selecting studies with the lowest risk of bias...
September 13, 2018: Current Medicinal Chemistry
Mehdi Ranjbar, Abbas Pardakhty, Arezou Amanatfard, Ali Asadipour
Metal-organic frameworks (MOFs) are structures made up of inorganic nodes, which can be either single ions or clusters of ions and organic linkers. This study reports on a novel processing route for producing β-estradiol encapsulated in Zn-MOF nanocomposites by microwave-assisted coprecipitation as a facile and fast method. Zn-MOF nanocomposites were synthesized with the aid of Zn(OAc)2 ⋅2H2 O and 2,6-pyridine dicarboxylic acid ammonium as an organic ligand. Furthermore, we studied encapsulated β-estradiol which is one of the most important classes of estrogenic compounds that are used in the treatment of prostate cancer and breast cancer...
2018: Drug Design, Development and Therapy
Karim Fizazi, Matthew R Smith, Bertrand Tombal
Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths among men. Androgen receptor (AR) signaling plays a key role in PC tumor growth and progression, with androgens stimulating PC proliferation and survival. Castration-resistant PC (CRPC) is characterized by increasing levels of prostate-specific antigen or radiographic progression despite androgen-deprivation therapy (ADT). In most patients, castration resistance results from aberrations in AR or the AR signaling pathway...
July 24, 2018: Clinical Genitourinary Cancer
Katriina J Peltola, Petri Bono, Robert Hugh Jones, Egils Vjaters, Pirjo Nykänen, Annamari Vuorela, Riikka Oksala, Pasi Pohjanjousi, Mika V J Mustonen, Karim Fizazi, Christophe Massard
BACKGROUND: Most prostate cancer patients develop castration-resistant prostate cancer (CRPC) after androgen deprivation therapy treatment. CRPC growth is mediated mostly by androgen receptor signalling driven by primary androgens synthesised largely by the CYP17A1 enzyme. OBJECTIVE: To evaluate the safety profile and dose-limiting toxicities of ODM-204. DESIGN, SETTING, AND PARTICIPANTS: In this open, uncontrolled, nonrandomised, multicentre, tolerability and pharmacokinetic first-in-man phase I dose escalation study, patients with metastatic CRPC were randomised to receive ODM-204 in sequential cohorts of five dose levels (ie, 50, 100, 200, 300, and 500mg twice daily) concomitantly with prednisone...
September 4, 2018: European Urology Focus
Pedro C Barata, Matthew Cooney, Prateek Mendiratta, Allison Tyler, Robert Dreicer, Jorge A Garcia
Introduction Ketoconazole is CYP-17 inhibitor with demonstrated activity in men with castration-resistant prostate cancer (CRPC). Lenalidomide is an antiangiogenic and immunomodulatory agent with broad antitumor activity. We hypothesized that the modulation of the cellular immune response to apoptosis caused by ketoconazole may be increased with the addition of lenalidomide. Methods This is an open-label, non-randomized, single-arm phase II study evaluating the efficacy and safety of the combination of ketoconazole and lenalidomide in patients with CRPC...
September 6, 2018: Investigational New Drugs
D Moran, T Gross, D Gavin, A J Costello
Recent advances in novel functional imaging techniques such as PSMA PET may now offer the ability to identify small volume metastases which may otherwise go undetected. The treatment of these lesions is controversial, particularly in the oligometastatic state. We report the case of an abdominal wall metastasis detected with PSMA imaging which we treated with surgical excision. This resulted in an undetectable PSA 6 weeks post excision.
September 5, 2018: Journal of Robotic Surgery
Emilie Jaune, Stéphane Rocchi
Metformin is the most common biguanide used in the treatment of diabetes, with 120 million treated patients worldwide. Metformin decreases hyperglycemia without inducing hypoglycemia in diabetic patients and is very well tolerated. The principal effects of metformin are to decrease hepatic gluconeogenesis and increase glucose absorption by skeletal muscles. These effects are primarily due to metformin's action on mitochondria, which requires the activation of metabolic checkpoint AMP-activated protein kinase (AMPK)...
2018: Frontiers in Endocrinology
Yang Su, Yue Liu, Christopher R Behrens, Scott Bidlingmaier, Nam-Kyung Lee, Rahul Aggarwal, Daniel W Sherbenou, Alma L Burlingame, Byron C Hann, Jeffry P Simko, Gayatri Premasekharan, Pamela L Paris, Marc A Shuman, Youngho Seo, Eric J Small, Bin Liu
Although initially responsive to androgen signaling inhibitors (ASIs), metastatic castration-resistant prostate cancer (mCRPC) inevitably develops and is incurable. In addition to adenocarcinoma (adeno), neuroendocrine prostate cancer (NEPC) emerges to confer ASI resistance. We have previously combined laser capture microdissection and phage antibody display library selection on human cancer specimens and identified novel internalizing antibodies binding to tumor cells residing in their tissue microenvironment...
September 6, 2018: JCI Insight
Yoo-Hun Noh
Although there is a clear need for improving men's health, treatment with suitable natural substances has not yet been well established. Previously, it was reported that MR-10, a novel complex of Korean dandelion and rooibos found by screening many natural products, improved sperm generation and activity. Here, the ability of MR-10 to increase testosterone levels and enhance men's health was tested. Treatment with MR-10 (400 mg/day) for a month significantly increased levels of free testosterone, total testosterone, and the testosterone precursor dehydroepiandrosterone by 22%, 14%, and 32%, respectively, in clinical studies...
September 4, 2018: Journal of Medicinal Food
Reynaldo Martina, Jos Houbiers, Joost Melis, Olivier van Till
There is a need for identifying effective drugs or terminating ineffective drugs as early as possible to optimize efficient and cost effective drug development. The aim of the proposed trial was to simultaneously establish Proof of Concept (PoC) and dose finding (DF) for a new drug with a novel mode of action in a new indication. We simulated and executed an adaptive allocation design to investigate the effects of a drug on male patients suffering from chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)...
September 3, 2018: Biometrical Journal. Biometrische Zeitschrift
Michael D Birnbaum, Ning Zhao, Balaji T Moorthy, Devang M Patel, Oleksandr N Kryvenko, Laine Heidman, Akhilesh Kumar, William M Morgan, Yuguang Ban, Isildinha M Reis, Xi Chen, Mark L Gonzalgo, Merce Jorda, Kerry L Burnstein, Fangliang Zhang
Most prostate cancer cases remain indolent for long periods of time, but metastatic progression quickly worsens the prognosis and leads to mortality. However, little is known about what promotes the metastasis of prostate cancer and there is a lack of effective prognostic indicators, making it immensely difficult to manage options for treatment or surveillance. Arginyltransferase 1 (Ate1) is the enzyme mediating post-translational protein arginylation, which has recently been identified as a master regulator affecting many cancer-relevant pathways including stress response, cell cycle checkpoints, and cell migration/adhesion...
September 3, 2018: Oncogene
Arpit Dheeraj, Chapla Agarwal, Isabel R Schlaepfer, David Raben, Rana Singh, Rajesh Agarwal, Gagan Deep
Background: Hypoxia in tumors is associated with resistance towards various therapies including radiotherapy. In this study, we assessed if hypoxia in cancer spheres could be effectively reduced by adding etomoxir (a β-oxidation inhibitor) immediately after cell irradiation. Methods: We employed cancer cells' sphere model to target hypoxia. Confocal imaging was used to analyze hypoxia and expression of specific biomarkers in spheres following various treatments (radiation and/or etomoxir)...
2018: Hypoxia
Alejandro Berlin, Jure Murgic, Ali Hosni, Melania Pintilie, Adriana Salcedo, Michael Fraser, Suzanne Kamel-Reid, Jingbin Zhang, Qiqi Wang, Carolyn Ch'ng, Samineh Deheshi, Elai Davicioni, Theodorus van der Kwast, Paul C Boutros, Robert G Bristow, Melvin L K Chua
BACKGROUND: The NCCN has recently endorsed the stratification of intermediate-risk prostate cancer (IR-PCa) into favorable and unfavourable subgourps, and recommend the addition of androgen deprivation therapy (ADT) to radiotherapy (RT) for unfavorable IR-PCa. Recently, more accurate prognostication was demonstrated by integrating a 22-feature genomic classifier (GC) to the NCCN stratification system. Here, we test the utility of the GC to better identify IR-PCa patients who are sufficiently treated by RT alone...
August 28, 2018: International Journal of Radiation Oncology, Biology, Physics
Agnieszka Latosinska, Maria Frantzi, Axel S Merseburger, Harald Mischak
Prostate cancer is one of the most commonly diagnosed malignancy and the fifth leading cause of cancer mortality in men. Despite the broad use of prostate-specific antigen test that resulted in an increase in number of diagnosed cases, disease management needs to be improved. Proteomic biomarkers alone and or in combination with clinical and pathological risk calculators are expected to improve on decreasing the unnecessary biopsies, stratify low risk patients, and predict response to treatment. To this end, significant efforts have been undertaken to identify novel biomarkers that can accurately discriminate between indolent and aggressive cancer forms and indicate those men at high risk for developing prostate cancer that require immediate treatment...
August 29, 2018: Diagnostics
Jens Staal, Rudi Beyaert
Prostate cancer is a highly prevalent form of cancer that is usually slow-developing and benign. Due to its high prevalence, it is, however, still the second most common cause of death by cancer in men in the West. The higher prevalence of prostate cancer in the West might be due to elevated inflammation from metabolic syndrome or associated comorbidities. NF-κB activation and many other signals associated with inflammation are known to contribute to prostate cancer malignancy. Inflammatory signals have also been associated with the development of castration resistance and resistance against other androgen depletion strategies, which is a major therapeutic challenge...
August 29, 2018: Cells
Vittorio Canale, Aleksandra Rak, Magdalena Kotańska, Joanna Knutelska, Agata Siwek, Marek Bednarski, Leszek Nowiński, Małgorzata Zygmunt, Paulina Koczurkiewicz, Elżbieta Pękala, Jacek Sapa, Paweł Zajdel
Benign prostatic hyperplasia (BPH) is the most common male clinical problem impacting the quality of life of older men. Clinical studies have indicated that the inhibition of α1A -/α1D adrenoceptors might offer effective therapy in lower urinary tract symptoms. Herein, a limited series of arylsulfonamide derivatives of (aryloxy)ethyl alicyclic amines was designed, synthesized, and biologically evaluated as potent α₁-adrenoceptor antagonists with uroselective profile. Among them, compound 9 (3-chloro-2-fluoro- N -([1-(2-(2-(2,2,2-trifluoroethoxy)phenoxy]ethyl)piperidin-4-yl)methyl)benzenesulfonamide) behaved as an α1A -/α1D -adrenoceptor antagonist ( K i (α₁) = 50 nM, EC50 (α1A ) = 0...
August 29, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Channing Paller, Hong Pu, Diane E Begemann, Cameron A Wade, Patrick J Hensley, Natasha Kyprianou
BACKGROUND: Prostate cancer progression is navigated by the androgen receptor (AR) and transforming-growth factor-β (TGF-β) signaling. We previously demonstrated that aberrant TGF-β signaling accelerates prostate tumor progression in a transgenic mouse model of prostate cancer via effects on epithelial-mesenchymal transition (EMT), driving castration-resistant prostate cancer (CRPC). METHODS: This study examined the antitumor effect of the combination of TGF-β receptor I (TβRI) inhibitor, galunisertib, and FDA-approved antiandrogen enzalutamide, in our pre-clinical model...
August 28, 2018: Prostate
Yuxiao Zheng, Yiren Gao, Xiao Li, Shuhui Si, Haoxiang Xu, Feng Qi, Jun Wang, Gong Cheng, Lixin Hua, Haiwei Yang
Background/purpose: Long non-coding RNAs (lncRNAs) have emerged as key molecules in initiation and progression of prostate cancer (PCa). In this study, we aimed to explore the role of lncRNA NAP1L6 in the development and progression of PCa. Materials and methods: We identified that lncRNA NAP1L6 was over-expressed both in PCa tissues and cell lines by gene expression array profiling. The expression level of NAP1L6 in 75 PCa tissues and adjacent tissues was detected by RT-PCR...
2018: OncoTargets and Therapy
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