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Mary-Ellen Taplin, Rana R McKay, Lillian Werner, Elahe A Mostaghel, Rosina T Lis, Olga Voznesensky, Zhenwei Zhang, Brett Marck, Alvin M Matsumoto, Liran Domachevsky, Katherine A Zukotynski, Manoj K Bhasin, Glenn J Bubley, Bruce Montgomery, Philip W Kantoff, Steven P Balk
PURPOSE: Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride. EXPERIMENTAL DESIGN: Eligible metastatic CRPC patients underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles...
September 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Thirupandiyur S Udayakumar, Radka Stoyanova, Mohammed M Shareef, Zhaomei Mu, Sakhi Philip, Kerry L Burnstein, Alan Pollack
Edelfosine is a synthetic alkyl-lysophospholipid that possesses significant antitumor activity in several human tumor models. Here, we investigated the effects of edelfosine combined with androgen deprivation (AD) in LNCaP and VCaP human prostate cancer cells. This treatment regimen greatly decreased cell proliferation compared with single agent or AD alone, resulting in higher levels of apoptosis in LNCaP compared with VCaP cells. Edelfosine caused a dose-dependent decrease in AKT activity, but did not affect the expression of total AKT in either cell line...
June 2016: Molecular Cancer Therapeutics
Vincent A DiPippo, Holly M Nguyen, Lisha G Brown, William C Olson, Robert L Vessella, Eva Corey
BACKGROUND: Despite multiple new therapies available to patients with advanced castration-resistant prostate cancer (CRPC), the overall survival benefit still remains relatively short. Therefore, it is important to investigate additional treatment options that could achieve greater efficacy. Because of tumor heterogeneity and the development of resistance to treatment with single agents, combination therapies using existing drugs with new agents can potentially broaden individual therapeutic windows and achieve improved efficacy and safety profiles...
February 15, 2016: Prostate
Xiaochuan Shan, Gwenn Danet-Desnoyers, Juan José Fung, Alan H Kosaka, Fraser Tan, Nicole Perfito, Joelle Lomax, Elizabeth Iorns
The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative seeks to address growing concerns about reproducibility in scientific research by conducting replications of recent papers in the field of prostate cancer. This Registered Report describes the proposed replication plan of key experiments from "Androgen Receptor Splice Variants Determine Taxane Sensitivity in Prostate Cancer" by Thadani-Mulero and colleagues (2014) published in Cancer Research in 2014. The experiment that will be replicated is reported in Fig...
2015: PeerJ
Eleni Efstathiou, Mark Titus, Sijin Wen, Anh Hoang, Maria Karlou, Robynne Ashe, Shi Ming Tu, Ana Aparicio, Patricia Troncoso, James Mohler, Christopher J Logothetis
BACKGROUND: Enzalutamide is a novel antiandrogen with proven efficacy in metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To evaluate enzalutamide's effects on cancer and on androgens in blood and bone marrow, and associate these with clinical observations. DESIGN, SETTING, AND PARTICIPANTS: In this prospective phase 2 study, 60 patients with bone mCRPC received enzalutamide 160mg orally daily and had transilial bone marrow biopsies before treatment and at 8 wk of treatment...
January 2015: European Urology
Maria Thadani-Mulero, Luigi Portella, Shihua Sun, Matthew Sung, Alexandre Matov, Robert L Vessella, Eva Corey, David M Nanus, Stephen R Plymate, Paraskevi Giannakakou
Prostate cancer growth depends on androgen receptor signaling. Androgen ablation therapy induces expression of constitutively active androgen receptor splice variants that drive disease progression. Taxanes are a standard of care therapy in castration-resistant prostate cancer (CRPC); however, mechanisms underlying the clinical activity of taxanes are poorly understood. Recent work suggests that the microtubule network of prostate cells is critical for androgen receptor nuclear translocation and activity. In this study, we used a set of androgen receptor deletion mutants to identify the microtubule-binding domain of the androgen receptor, which encompasses the DNA binding domain plus hinge region...
April 15, 2014: Cancer Research
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