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Enzalutamide resistance

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https://www.readbyqxmd.com/read/27915475/how-precisely-can-prostate-cancer-be-managed
#1
REVIEW
Liyan Zhuang, Matthew T Johnson
Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2- ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27909718/enzalutamide-inhibits-proliferation-of-gemcitabine-resistant-bladder-cancer-cells-with-increased-androgen-receptor-expression
#2
Koji Kameyama, Kengo Horie, Kosuke Mizutani, Taku Kato, Yasunori Fujita, Kyojiro Kawakami, Toshio Kojima, Tatsuhiko Miyazaki, Takashi Deguchi, Masafumi Ito
Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling...
November 24, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27900064/enzalutamide-induced-acute-generalized-exanthematous-pustulosis
#3
Chloé Alberto, Maria Polina Konstantinou, Catherine Martinage, Eline Casassa, Emilie Tournier, Haleh Bagheri, Vincent Sibaud, Loïc Mourey, Juliette Mazereeuw-Hautier, Nicolas Meyer, Carle Paul, Cristina Bulai Livideanu
INTRODUCTION: Enzalutamide (Xtandi®) is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013. OBJECTIVE: We report the first case of acute generalized exanthematous pustulosis (AGEP) induced by enzalutamide. OBSERVATION: A 62-year-old male patient with no significant medical history, was diagnosed in April 2014 with metastatic prostatic adenocarcinoma...
November 13, 2016: Journal of Dermatological Case Reports
https://www.readbyqxmd.com/read/27897170/truncation-and-constitutive-activation-of-the-androgen-receptor-by-diverse-genomic-rearrangements-in-prostate-cancer
#4
Christine Henzler, Yingming Li, Rendong Yang, Terri McBride, Yeung Ho, Cynthia Sprenger, Gang Liu, Ilsa Coleman, Bryce Lakely, Rui Li, Shihong Ma, Sean R Landman, Vipin Kumar, Tae Hyun Hwang, Ganesh V Raj, Celestia S Higano, Colm Morrissey, Peter S Nelson, Stephen R Plymate, Scott M Dehm
Molecularly targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signalling undermines therapeutic efficacy and promotes progression to lethal castration-resistant prostate cancer (CRPC), even when patients are treated with potent second-generation AR-targeted therapies abiraterone and enzalutamide. Here we define diverse AR genomic structural rearrangements (AR-GSRs) as a class of molecular alterations occurring in one third of CRPC-stage tumours...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27892725/investigational-serine-threonine-kinase-inhibitors-against-prostate-cancer-metastases
#5
Claudio Festuccia
INTRODUCTION: Androgen deprivation therapy (ADT) is used as first therapeutic approach in prostate cancer (PCa) although castration resistant disease (CRPC) develops with high frequency. CRPC is the consequence of lack of apoptotic responses to ADT. Alternative targeting of the androgen axis with abiraterone and enzalutamide, as well as taxane-based chemotherapy were used in CRPC. Serine/threonine protein kinases (STKs) regulate different molecular pathways of normal and neoplastic cells and participate to development of CRPC as well as to the progression towards a bone metastatic disease (mCRPC)...
November 28, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27890446/efficacy-of-therapies-after-galeterone-in-patients-with-castration-resistant-prostate-cancer
#6
Rana R McKay, Lillian Werner, Matthew Fiorillo, Jennifer Roberts, Elisabeth I Heath, Glenn J Bubley, Robert Bruce Montgomery, Mary-Ellen Taplin
BACKGROUND: Galeterone is a multi-targeted agent with activity as a CYP17 inhibitor, androgen receptor antagonist, and also causes androgen receptor degradation. It has shown meaningful anti-tumor activity with a well-tolerated safety profile in patients with castration-resistant prostate cancer (CRPC) in phase I and II studies; however, the efficacy of currently approved CRPC therapies after treatment with galeterone is unknown. In this study, we evaluate prostate specific antigen (PSA) response of non-protocol therapies following galeterone in a subset of patients treated on the Androgen Receptor Modulation Optimized for Response (ARMOR) 2 study...
October 27, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27885457/-psma-targeted-radioligand-therapy-in-prostate-cancer
#7
M M Heck, M Retz, R Tauber, K Knorr, C Kratochwil, M Eiber
Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany...
November 24, 2016: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27876504/disease-and-treatment-characteristics-of-men-diagnosed-with-metastatic-hormone-sensitive-prostate-cancer-in-real-life-analysis-from-a-commercial-claims-database
#8
Thomas W Flaig, Ravi C Potluri, Yvette Ng, Mary B Todd, Maneesha Mehra, Celestia S Higano
BACKGROUND: Our understanding of the clinical characteristics and treatment patterns of men who present with newly diagnosed metastatic (M1) hormone-sensitive prostate cancer is based mainly on clinical trial data. We sought to characterize the M1 population seen in routine clinical practice using a commercial claims database. PATIENTS AND METHODS: A US claims (2000-2013) database was used to identify patients with an index diagnosis of prostate cancer. M1 patients were identified by "International Classification of Diseases, 9th revision, Clinical Modification" diagnosis codes of metastasis to bone, viscera, distant lymph node, and unspecified sites within 90 days of the prostate cancer diagnosis...
October 18, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27872478/circulating-tumour-cells-as-biomarkers-of-prostate-bladder-and-kidney-cancer
#9
REVIEW
Michael A Gorin, James E Verdone, Emma van der Toom, Trinity J Bivalacqua, Mohamad E Allaf, Kenneth J Pienta
Circulating tumour cells (CTCs) have been studied as biomarkers of a number of solid malignancies. Potential clinical applications for CTC analysis include early cancer detection, disease staging, monitoring for recurrence, prognostication, and to aid in the selection of therapy. In the field of urologic oncology, CTCs have been most widely studied as prognostic biomarkers of castration-resistant prostate cancer. Additionally, emerging data support a role for CTCs to help identify which patients are most likely to respond to novel androgen-pathway targeted therapies, such as abiraterone and enzalutamide...
November 22, 2016: Nature Reviews. Urology
https://www.readbyqxmd.com/read/27823639/prostate-cancer-perspectives-after-chaarted-optimizing-treatment-sequence
#10
REVIEW
Sergio Vázquez Estévez, Urbano Anido Herranz, Ovidio Fernández Calvo, Francisco Javier Afonso Afonso, Lucía Santomé Couto, Martín Lázaro Quintela, Luis León Mateos, Sonia Maciá Escalante
Prostate cancer is the most frequent cancer amongst men. Until recently, only two therapeutic options, initial androgen-deprivation therapy in patients without castration-resistant prostate cancer, with addition of docetaxel when the disease becomes castration-resistant, were considered as standard. In the last years, new drugs (abiraterone, enzalutamide, Ra-223, Sipuleucel) have been developed for prostate cancer treatment with important advantages in safety and efficacy. Results from the recent Chaarted study, in patients that received docetaxel for the hormone sensitive disease, have contributed to change the initial treatment approach in metastatic prostate cancer, in order to adapt the best sequence for each patient...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27822685/sequencing-treatment-for-castration-resistant-prostate-cancer
#11
REVIEW
Catherine E Handy, Emmanuel S Antonarakis
Prostate cancer is the most common non-cutaneous cancer diagnosed in men and the second leading cause of male cancer deaths in the USA. While most cases are diagnosed in early stages, some will present as or progress to metastatic disease and eventually castration-resistant prostate cancer (mCRPC) which has a mortality rate exceeding 50 %. There are currently six approved systemic life-prolonging therapies for use in mCRPC, yet little data to guide sequencing. Clinical factors, including the presence or absence of symptoms and the presence or absence of visceral metastases, should help determine the best therapeutic choice at each treatment node...
December 2016: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/27815387/polycomb-mediated-disruption-of-an-androgen-receptor-feedback-loop-drives-castration-resistant-prostate-cancer
#12
Ka Wing Fong, Jonathan C Zhao, Jung Kim, Shangze Li, Yeqing Angela Yang, Bing Song, Laure Rittié, Ming Hu, Ximing J Yang, Bernard Perbal, Jindan Yu
The lethal phenotype of castration-resistant prostate cancer (CRPC) is generally caused by augmented signaling from the androgen receptor (AR). Here we report that the AR-repressed gene CCN3/NOV inhibits AR signaling and acts in a negative feedback loop to block AR function. Mechanistically, a cytoplasmic form of CCN3 interacted with the AR N-terminal domain to sequester AR in the cytoplasm of prostate cancer cells, thereby reducing AR transcriptional activity and inhibiting cell growth. However, constitutive repression of CCN3 by the Polycomb group protein EZH2 disrupted this negative feedback loop in both CRPC and enzalutamide-resistant prostate cancer cells...
November 4, 2016: Cancer Research
https://www.readbyqxmd.com/read/27815035/combination-of-sorafenib-and-enzalutamide-as-a-potential-new-approach-for-the-treatment-of-castration-resistant-prostate-cancer
#13
Hongxi Wu, Lulu Zhang, Xiaofang Gao, Xiuna Zhang, Jingjing Duan, Linjun You, Yan Cheng, Jinsong Bian, Qingyi Zhu, Yong Yang
Enzalutamide, a novel androgen receptor (AR) antagonist, prolongs overall survival of patients with castration-resistant prostate cancer (CRPC); however, patients eventually progress with enzalutamide resistance. We studied the efficacy of sorafenib combined with enzalutamide in a CRPC model and explored a potential strategy to improve enzalutamide efficacy in vitro and in LNCaP xenografts. The results indicated that enzalutamide combined with sorafenib potently decreased cell proliferation and induced apoptosis in the prostate cancer cell lineLNCaP...
November 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27804988/prostate-cancer-ar-aberrations-and-resistance-to-abiraterone-or-enzalutamide
#14
Gerhardt Attard, Emmanuel S Antonarakis
No abstract text is available yet for this article.
December 2016: Nature Reviews. Urology
https://www.readbyqxmd.com/read/27799360/androgen-receptor-signaling-in-castration-resistant-prostate-cancer-a-lesson-in-persistence
#15
Isabel Coutinho, Tanya Day, Wayne D Tilley, Luke A Selth
The androgen receptor (AR) signaling axis drives all stages of prostate cancer, including the lethal, drug-resistant form of the disease termed castration resistant prostate cancer (CRPC), which arises following failure of androgen deprivation therapy (ADT). Persistent AR activity in spite of ADT and the second-generation AR-targeting agents enzalutamide and abiraterone is achieved in many cases via direct alterations to the AR. Indeed, the role of AR in prostate cancer represents an archetype of therapy-mediated selection pressure and oncogene addiction...
October 31, 2016: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27793943/consequences-of-an-early-psa-response-to-enzalutamide-treatment-for-japanese-patients-with-metastatic-castration-resistant-prostate-cancer
#16
Haruo Kato, Yosuke Furuya, Yoshiyuki Miyazawa, Takeshi Miyao, Takahiro Syuto, Masashi Nomura, Yoshitaka Sekine, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuto Ito, Kazuhiro Suzuki
BACKGROUND/AIM: Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. PATIENTS AND METHODS: Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27790145/systemic-immune-inflammation-index-predicts-the-clinical-outcome-in-patients-with-mcrpc-treated-with-abiraterone
#17
Cristian Lolli, Orazio Caffo, Emanuela Scarpi, Michele Aieta, Vincenza Conteduca, Francesca Maines, Emanuela Bianchi, Francesco Massari, Antonello Veccia, Vincenzo E Chiuri, Gaetano Facchini, Ugo De Giorgi
Background: A systemic immune-inflammation index (SII) based on neutrophil (N), lymphocyte (L), and platelet (P) counts has shown a prognostic impact in several solid tumors. The aim of this study is to evaluate the prognostic role of SII in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone post docetaxel. Patients and Methods: We retrospectively reviewed consecutive mCRPC patients treated with abiraterone after docetaxel in our Institutions. X-tile 3.6.1 software, cut-off values of SII, neutrophil-to-lymphocyte ratio (NLR) defined as N/L and platelets-to-lymphocyte ratio (PLR) as P/L...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27787354/targeting-the-androgenic-pathway-in-elderly-patients-with-castration-resistant-prostate-cancer-a-meta-analysis-of-randomized-trials
#18
Giandomenico Roviello, Maria Rosa Cappelletti, Laura Zanotti, Angela Gobbi, Chiara Senti, Alberto Bottini, Andrea Ravelli, Alberto Bonetta, Giovanni Paganini, Daniele Generali
BACKGROUND: The novel hormonal drugs have recently entered in the armamentarium of therapies for treatment of metastatic castration-resistant prostate cancer (CRPC). First reports are available for their use in elderly men with CRPC. METHOD: A meta-analysis of randomized controlled trials (RCTs) has been performed. PubMed, the Cochrane Library, and American Society of Clinical Oncology (ASCO) University Meeting were searched for data on the use of new hormonal treatment in elderly patients with CRPC...
October 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27773999/role-of-chemotherapy-and-mechanisms-of-resistance-to-chemotherapy-in-metastatic-castration-resistant-prostate-cancer
#19
Vipin Lohiya, Jeanny B Aragon-Ching, Guru Sonpavde
Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide...
2016: Clinical Medicine Insights. Oncology
https://www.readbyqxmd.com/read/27765852/targeting-binding-function-3-of-the-androgen-receptor-blocks-its-co-chaperone-interactions-nuclear-translocation-and-activation
#20
Nada Lallous, Eric Leblanc, Ravi S N 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 antiandrogens, such as enzalutamide, or androgen synthesis inhibitors like abiraterone has improved patient outcomes in the treatment of advanced prostate cancer. However, due to the development of drug resistance and tumor cell survival, a 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...
December 2016: Molecular Cancer Therapeutics
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