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Novel treatments prostate

Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
October 17, 2016: Oncotarget
Nada Lallous, Eric Leblanc, Ravi Sn Munuganti, Mohamed D H Hassona, Nader Al Nakouzi, Shannon Awrey, Helene Morin, Mani Roshan-Moniri, Kriti Singh, Sam Lawn, Takeshi Yamazaki, Hans H Adomat, Christophe Andre, Mads Daugaard, Robert N Young, Emma S Tomlinson Guns, Paul S Rennie, Artem Cherkasov
The development of new anti-androgens such as enzalutamide or androgen synthesis inhibitors like abiraterone have improved patient outcomes in the treatment of advanced prostate cancer (PCa). However, due to the development of drug resistance and tumor cell survival, the majority of these patients progress to the refractory state of castration-resistant prostate cancer (CRPC). Thus, newer therapeutic agents and a better understanding of their mode of action are needed for treating these CRPC patients. We demonstrated previously that targeting the Binding Function 3 (BF3) pocket of the androgen receptor (AR) has great potential for treating patients with CRPC...
October 7, 2016: Molecular Cancer Therapeutics
Ion Cristobal, Blanca Torrejón, Manuel Pedregal, Federico G Rojo, Jesús García-Foncillas
Dear Editor, We have read with great interest the recent published manuscript by Caiazza et al. (2016), which provides novel exciting findings about the potential therapeutic value of enzalutamide in patients with androgen receptor (AR)-positive triple negative breast cancer (TNBC). Some previous studies have shown promising antitumor effects of this drug in breast tumors. Thus, enzalutamide-mediated AR inhibition has been reported to reduce proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis of TNBC cells in vitro and decrease viability of TNBC xenografts in vivo (Cochrane et al...
October 20, 2016: Endocrine-related Cancer
G Magistro, C G Stief, C Gratzke
Novel minimally invasive treatment options for the management of male lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO) aim to provide equal efficacy compared to standard techniques with a more favourable safety profile. The preservation of all aspects of male sexual function including antegrade ejaculation is increasingly important to patients. It should be ideally performed in an outpatient setting under local anesthesia to assure a short recovery time. Novel injectables for intraprostatic application (botulinum neurotoxin A, NX-1207, PRX302) have emerged and first phase III results could not confirm the promising initial data...
October 19, 2016: Der Urologe. Ausg. A
Claire Levrier, Martin C Sadowski, Anja Rockstroh, Brian Gabrielli, Maria Kavallaris, Melanie Lehman, Rohan A Davis, Colleen C Nelson
The lack of a cure for metastatic castrate-resistant prostate cancer (mCRPC) highlights the urgent need for more efficient drugs to fight this disease. Here, we report the mechanism of action of the natural product 6α-acetoxyanopterine (6-AA) in prostate cancer cells. At low nanomolar doses, this potent cytotoxic alkaloid from the Australian endemic tree Anopterus macleayanus induced a strong accumulation of LNCaP and PC-3 (prostate cancer) cells as well as HeLa (cervical cancer) cells in mitosis, severe mitotic spindle defects and asymmetric cell divisions, ultimately leading to mitotic catastrophe accompanied by cell death through apoptosis...
October 19, 2016: Molecular Cancer Therapeutics
Zheng Zhang, Bo Jin, Yaqiong Jin, Shengquan Huang, Xiaohua Niu, Zebin Mao, Dianqi Xin
Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex...
October 15, 2016: Experimental Cell Research
Alessio Soggiu, Cristian Piras, Viviana Greco, Paola Devoto, Andrea Urbani, Luigino Calzetta, Marco Bortolato, Paola Roncada
The enzyme 5α-reductase (5αR) catalyzes the conversion of progesterone and testosterone into neuroactive steroids implicated in a wide array of behavioral functions. The prototypical 5αR inhibitor, finasteride (FIN), is clinically approved for the treatment of androgenic alopecia and benign prostatic hyperplasia. Recent evidence has shown that FIN, albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia...
October 6, 2016: Psychoneuroendocrinology
Xingwang Jia, Jing Chen, Shisheng Sun, Weiming Yang, Shuang Yang, Punit Shah, Naseruddin Hoti, Bob Veltri, Hui Zhang
Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. The blood Prostate-Specific Antigen (PSA) test has facilitated early detection and intervention of prostate cancer. However, blood PSA levels are less effective in distinguishing aggressively from indolent prostate cancers and other benign prostatic diseases. Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressively from indolent disease remains an urgent medical need...
October 17, 2016: Proteomics
Michael S Leapman, Peter R Carroll
INTRODUCTION: Selective treatment approaches for prostate cancer (PCa) are warranted given the highly varied nature of the disease and the consequences associated with definitive therapy. MATERIALS AND METHODS: We present a stepwise overview of strategies to not treat PCa, ranging from improved early detection practices that seek to improve the yield at initial diagnosis, as well as refinements to risk prediction and the performance of active surveillance. RESULTS: Adherence to screening guidelines is non-uniform...
October 13, 2016: Urologic Oncology
Che-Kai Tsao, John Sfakianos, Bobby Liaw, Kiev Gimpel-Tetra, Margaret Kemeny, Linda Bulone, Mohammad Shahin, William Kyu Oh, Matthew David Galsky
LESSONS LEARNED: The safety and activity findings of abiraterone acetate plus prednisone treatment in black men with mCRPC were similar to results from previously conducted studies with largely white populations.Poor trial accrual continues to be a challenge in black men with mCRPC and further efforts are needed to address such underrepresentation. BACKGROUND: Self-identified black men have higher incidence and mortality from prostate cancer in the United States compared with white men but are dramatically underrepresented in clinical trials exploring novel therapies for metastatic castration-resistant prostate cancer (mCRPC)...
October 14, 2016: Oncologist
Tsuyoshi Hamada, NaNa Keum, Reiko Nishihara, Shuji Ogino
Molecular pathological epidemiology (MPE) is an integrative field that utilizes molecular pathology to incorporate interpersonal heterogeneity of a disease process into epidemiology. In each individual, the development and progression of a disease are determined by a unique combination of exogenous and endogenous factors, resulting in different molecular and pathological subtypes of the disease. Based on "the unique disease principle," the primary aim of MPE is to uncover an interactive relationship between a specific environmental exposure and disease subtypes in determining disease incidence and mortality...
October 13, 2016: Journal of Gastroenterology
Daeyong Jin, Hyunju Lee
MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of target genes, and they are involved in cancer initiation and progression. Even though many cancer-related miRNAs were identified, their functional impact may vary, depending on their effects on the regulation of other miRNAs and genes. In this study, we propose a novel method for the prioritization of candidate cancer-related miRNAs that may affect the expression of other miRNAs and genes across the entire biological network. For this, we propose three important features: the average expression of a miRNA in multiple cancer samples, the average of the absolute correlation values between the expression of a miRNA and expression of all genes, and the number of predicted miRNA target genes...
October 13, 2016: Scientific Reports
Domenico Albino, Gianluca Civenni, Simona Rossi, Abhishek Mitra, Carlo V Catapano, Giuseppina M Carbone
Metastatic prostate cancer represents a yet unsolved clinical problem due to the high frequency of relapse and treatment resistance. Understanding the pathways that lead to prostate cancer progression is an important task to prevent this deadly disease. The ETS transcription factor ESE3/EHF has an important role in differentiation of human prostate epithelial cells. Loss of ESE3/EHF in prostate epithelial cells determines transformation, epithelial-to-mesenchymal transition (EMT) and acquisition of stem-like properties...
October 8, 2016: Oncotarget
Shingo Hatakeyama, Tohru Yoneyama, Yuki Tobisawa, Chikara Ohyama
The application of prostate-specific antigen (PSA) in prostate cancer (PC) screening, diagnosis, and prognosis has improved the clinical management of PC patients. However, the PSA assay has been faced with criticism due to its potential association with over-diagnosis and subsequent overtreatment of patients with indolent disease. The United States Preventive Services Task Force incited much debate over PSA-based screening in 2012 by recommending against this approach. However, the PSA assay remains the first-line tool for the early detection of PC...
October 11, 2016: International Journal of Clinical Oncology
Ian R Logan, Urszula L McClurg, Dominic L Jones, Daniel J O'Neill, Fadhel S Shaheen, John Lunec, Luke Gaughan, Craig N Robson
Inhibition of androgen receptor (AR) signalling represents the conventional medical management of prostate cancer. Ultimately this treatment fails because tumors develop an incurable, castrate resistant phenotype, resulting in an unmet need for new treatments in prostate cancer. The AR remains a viable therapeutic target in castrate resistant disease, such that novel ways of downregulating AR activities are attractive as potential treatments. Here we describe a mechanism by which the AR can be downregulated by the MDM2 antagonist Nutlin-3, resulting in loss of pro-survival c-FLIP gene expression and apoptosis...
October 9, 2016: Oncotarget
Edel McCrea, Tristan M Sissung, Douglas K Price, Cindy H Chau, William D Figg
Significant therapeutic progress has been made in treating prostate cancer in recent years. Drugs such as enzalutamide, abiraterone, and cabazitaxel have expanded the treatment armamentarium, although it is not completely clear which of these drugs are the most-effective option for individual patients. Moreover, such advances have been tempered by the development of therapeutic resistance. The purpose of this review is to summarize the current literature pertaining to the biochemical effects of AR variants and their consequences on prostate cancer therapies at both the molecular level and in clinical treatment...
October 7, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Bhumika Wadhwa, Rashmi Dumbre
Prostate (CaP) cancer is the second-leading cause of cancer-related mortality in men in Western societies. Androgen receptor (AR) signaling is a critical survival pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. Although a majority of patients initially respond to ADT, most will eventually develop castrate resistance. The recent discovery that AR signaling persists during systemic castration via intratumoral production of androgens led to the development of novel anti-androgen therapies...
October 6, 2016: Chemico-biological Interactions
Hesham Fathy Hassan Hassan, Ahmed Mohamed Mansour, Amira Morad Hussein Abo-Youssef, Bakheet E M Elsadek, Basim Anwar Shehata Messiha
Currently, the outcomes of conventional chemotherapeutic approaches are unsatisfactory. Clinical application of nanoparticles seems promising. We aim to evaluate the possible antitumor activity of zinc oxide nanoparticles (ZnONPs) as a chemotherapeutic approach in in vitro and in vivo experimental models. An in vitro study was performed on three different cell lines, namely human hepatocellular carcinoma (HEPG2), human prostate cancer (PC3), and none-small cell lung cancer (A549) cell lines. An in vivo study using diethylnitrosamine (DENA)-induced HCC in adult male Wistar rats was conducted to investigate the potential antitumor activity of ZnONPs in HCC and the possible underlying mechanisms...
October 8, 2016: Clinical and Experimental Pharmacology & Physiology
Kevin M Koo, Eugene J H Wee, Paul N Mainwaring, Yuling Wang, Matt Trau
Cancer is a heterogeneous disease which manifests as different molecular subtypes due to the complex nature of tumor initiation, progression, and metastasis. The concept of precision medicine aims to exploit this cancer heterogeneity by incorporating diagnostic technology to characterize each cancer patient's molecular subtype for tailored treatments. To characterize cancer molecular subtypes accurately, a suite of multiplexed bioassays have currently been developed to detect multiple oncogenic biomarkers. Despite the reliability of current multiplexed detection techniques, novel strategies are still needed to resolve limitations such as long assay time, complex protocols, and difficulty in interpreting broad overlapping spectral peaks of conventional fluorescence readouts...
September 26, 2016: Small
Nora Sundahl, Dorien Clarisse, Marc Bracke, Fritz Offner, Wim Vanden Berghe, Ilse M Beck
Although adverse effects and glucocorticoid resistance cripple their chronic use, glucocorticoids form the mainstay therapy for acute and chronic inflammatory disorders, and play an important role in treatment protocols of both lymphoid malignancies and as adjuvant to stimulate therapy tolerability in various solid tumors. Glucocorticoid binding to their designate glucocorticoid receptor (GR), sets off a plethora of cell-specific events including therapeutically desirable effects, such as cell death, as well as undesirable effects, including chemotherapy resistance, systemic side effects and glucocorticoid resistance...
2016: Oncoscience
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