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Metastatic castrate resistant prostate cancer

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https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#1
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#2
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28318331/docetaxel-chemotherapy-in-metastatic-castration-resistant-prostate-cancer-cost-of-care-in-medicare-and-commercial-populations
#3
A Armstrong, C Bui, K Fitch, T Goss Sawhney, B Brown, S Flanders, M Balk, J Deangelis, J Chambers
OBJECTIVE: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We used Medicare 5% sample and MarketScan® Commercial (2010 - 2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date...
March 20, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28315704/interleukin-6-and-prostate-cancer-current-developments-and-unsolved-questions
#4
Zoran Culig, Martin Puhr
Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models...
March 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28314838/a-phase-i-study-of-abiraterone-acetate-combined-with-bez235-a-dual-pi3k-mtor-inhibitor-in-metastatic-castration-resistant-prostate-cancer
#5
Xiao X Wei, Andrew C Hsieh, Won Kim, Terence Friedlander, Amy M Lin, Mirela Louttit, Charles J Ryan
LESSONS LEARNED: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored. BACKGROUND: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28314611/clinical-outcomes-from-androgen-signaling-directed-therapy-after-treatment-with-abiraterone-acetate-and-prednisone-in-patients-with-metastatic-castration-resistant-prostate-cancer-post-hoc-analysis-of-cou-aa-302
#6
Matthew R Smith, Fred Saad, Dana E Rathkopf, Peter F A Mulders, Johann S de Bono, Eric J Small, Neal D Shore, Karim Fizazi, Thian Kheoh, Jinhui Li, Peter De Porre, Mary B Todd, Margaret K Yu, Charles J Ryan
In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302...
March 14, 2017: European Urology
https://www.readbyqxmd.com/read/28314320/the-clinical-efficacy-of-enzalutamide-in-metastatic-prostate-cancer-prospective-single-center-study
#7
Giuseppe Cicero, Rossella DE Luca, Patrizia Dorangricchia, Francesco Dieli
BACKGROUND/AIM: To evaluate the effectiveness of enzalutamide in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer, progressing after chemotherapy with docetaxel plus prednisone. PATIENTS AND METHODS: A total of 60 patients were enrolled. Reduction in serum prostate-specific antigen (PSA) was assessed as the primary endpoint, while reduction in pain, safety, progression-free survival and overall survival represented secondary endpoints...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28297567/developing-a-novel-two-dimensional-culture-system-to-enrich-human-prostate-luminal-progenitors-that-can-function-as-a-cell-of-origin-for-prostate-cancer
#8
Dingxiao Zhang, Kevin Lin, Yue Lu, Kiera Rycaj, Yi Zhong, Hsueh-Ping Chao, Tammy Calhoun-Davis, Jianjun Shen, Dean G Tang
Elucidating the cell of origin of cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells in the normal human prostate (NHP) can function as the cell of origin for prostate cancer (PCa). Here, we show that the organoids derived from bulk NHP luminal cells can also be tumorigenically transformed. We further show that the WIT medium, which is used to culture human mammary epithelial progenitor cells, when combined with the ROCK inhibitor, can readily propagate a population of progenitor-like cells from the primary NHP luminal cell isolates...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28295408/circulating-tumor-cells-as-a-marker-for-progression-free-survival-in-metastatic-castration-na%C3%A3-ve-prostate-cancer
#9
Andreas Josefsson, Anna Linder, Despina Flondell Site, Giacomo Canesin, Anna Stiehm, Aseem Anand, Anders Bjartell, Jan-Erik Damber, Karin Welén
BACKGROUND: Analysis of circulating tumor cells (CTC) is a promising prognostic marker in castration-resistant prostate cancer (CRPC). The aim of this study was to investigate CTC detection and phenotyping as prognostic biomarkers for response to primary androgen deprivation therapy (ADT) of metastatic prostate cancer (PC). METHODS: PC patients presenting with a prostate specific antigen (PSA) >80 ng/ml and/or metastatic disease, intended for ADT were enrolled in the study...
March 10, 2017: Prostate
https://www.readbyqxmd.com/read/28291739/a-radiobiological-model-of-metastatic-burden-reduction-for-molecular-radiotherapy-application-to-patients-with-bone-metastases
#10
Ana M Denis-Bacelar, Sarah J Chittenden, Iain Murray, Antigoni Divoli, V Ralph McCready, David P Dearnaley, Joe M O'Sullivan, Bernadette Johnson, Glenn D Flux
Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient...
April 7, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28285412/symptoms-and-impacts-in-non-metastatic-castration-resistant-prostate-cancer-qualitative-study-findings
#11
Erin L Tomaszewski, Pierre Moise, Robert N Krupnick, Jared Downing, Margaret Meyer, Shevani Naidoo, Stefan Holmstrom
OBJECTIVES: We developed a conceptual model to define key concepts associated with patients' experiences with the signs, symptoms, and impacts of non-metastatic castration-resistant prostate cancer (M0-CRPC). METHODS: A targeted review of peer-reviewed literature, and other publicly available information, identified and categorized symptoms and impacts related to early-stage prostate cancer. Semi-structured interviews with five clinical experts helped determine the most relevant and important concepts for patients with M0-CRPC...
March 11, 2017: Patient
https://www.readbyqxmd.com/read/28283376/navigating-the-evolving-therapeutic-landscape-in-advanced-prostate-cancer
#12
REVIEW
E David Crawford, Daniel Petrylak, Oliver Sartor
Prostate cancer is the most common cause of cancer in men, with 137.9 new cases per 100,000 men per year. The overall 5-year survival rate for prostate cancer is very high. Up to 20% of men who undergo state-of-the art treatment for prostate cancer will develop castration-resistant prostate cancer (CRPC) within 5 years, with median survival for those with metastatic CRPC ranging from approximately 15 to 36 months in recent studies. With the advent of several new drugs in the past 5 years to treat CRPC, the challenge facing clinicians is how to best sequence or combine therapies or both to optimize outcomes...
March 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28283282/custirsen-in-combination-with-docetaxel-and-prednisone-for-patients-with-metastatic-castration-resistant-prostate-cancer-synergy-trial-a-phase-3-multicentre-open-label-randomised-trial
#13
Kim N Chi, Celestia S Higano, Brent Blumenstein, Jean-Marc Ferrero, James Reeves, Susan Feyerabend, Gwenaelle Gravis, Axel S Merseburger, Arnulf Stenzl, Andries M Bergman, Som D Mukherjee, Pawel Zalewski, Fred Saad, Cindy Jacobs, Martin Gleave, Johann S de Bono
BACKGROUND: Clusterin is a chaperone protein associated with treatment resistance and upregulated by apoptotic stressors such as chemotherapy. Custirsen is a second-generation antisense oligonucleotide that inhibits clusterin production. The aim of the SYNERGY trial was to investigate the effect of custirsen in combination with docetaxel and prednisone on overall survival in patients with metastatic castration-resistant prostate cancer. METHODS: SYNERGY was a phase 3, multicentre, open-label, randomised trial set at 134 study centres in 12 countries...
March 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28282611/phase-ib-dose-finding-study-of-abiraterone-acetate-plus-buparlisib-bkm120-or-dactolisib-bez235-in-patients-with-castration-resistant-prostate-cancer
#14
Christophe Massard, Kim Nguyen Chi, Daniel Castellano, Johann de Bono, Gwenaelle Gravis, Luc Dirix, Jean-Pascal Machiels, Alain Mita, Begona Mellado Gonzalez, Sabine Turri, Joan Maier, Denes Csonka, Arunava Chakravartty, Karim Fizazi
BACKGROUND: The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signalling axis and androgen receptor (AR) pathways exhibit reciprocal feedback regulation in phosphatase and tensin homologue (PTEN)-deficient metastatic castration-resistant prostate cancer (CRPC) in preclinical models. This phase Ib study evaluated the pan-PI3K inhibitor buparlisib (BKM120) and the dual pan-PI3K/ mammalian target of rapamycin (mTOR) inhibitor dactolisib (BEZ235) in combination with abiraterone acetate (AA) in patients with CRPC...
March 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28280855/repeated-psma-targeting-radioligand-therapy-of-metastatic-prostate-cancer-with-131-i-mip-1095
#15
Ali Afshar-Oromieh, Uwe Haberkorn, Christian Zechmann, Thomas Armor, Walter Mier, Fabian Spohn, Nils Debus, Tim Holland-Letz, John Babich, Clemens Kratochwil
PURPOSE: Prostate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies. METHODS: Thirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with (131)I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy...
March 9, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28278515/phase-2-study-of-circulating-microrna-biomarkers-in-castration-resistant-prostate-cancer
#16
Hui-Ming Lin, Kate L Mahon, Calan Spielman, Howard Gurney, Girish Mallesara, Martin R Stockler, Patricia Bastick, Karen Briscoe, Gavin Marx, Alexander Swarbrick, Lisa G Horvath
BACKGROUND: Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings. METHODS: Using real-time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients...
March 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28278075/piecing-the-puzzle-together-docetaxel-cycles-and-current-considerations-in-the-treatment-of-metastatic-castration-resistant-prostate-cancer
#17
Hannah E Feinman, Douglas K Price, William D Figg
Docetaxel is the current first line therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is no standard number of docetaxel cycles given to patients. In their post hoc analysis of the Mainsail study, de Morrée et al. show that the number of docetaxel cycles administered to a patient is a significant factor contributing to overall survival. These findings warrant further investigation into the standardization of the number of docetaxel cycles administered.
February 25, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28277852/the-treatment-patterns-of-castration-resistant-prostate-cancer-in-japan-including-symptomatic-skeletal-events-and-associated-treatment-and-healthcare-resource-use
#18
Hiroji Uemura, Marco DiBonaventura, Ed Wang, Dianne Athene Ledesma, Kristen Concialdi, Yasuko Aitoku
BACKGROUND: Real-world treatment patterns of bone metastatic castration-resistant prostate cancer (mCRPC) in Japan were examined, focusing on treatment patterns and resource use differences attributed to symptomatic skeletal events (SSEs). METHODS: Urologists (N=176) provided retrospective chart data for patients with mCRPC (N=445) via online surveys. Descriptive analyses and chi-square tests evaluated treatment patterns and their differences by SSE presence; generalized linear mixed models examined healthcare resource utilization differences as a function of SSEs...
March 6, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28275218/epigenomic-regulation-of-androgen-receptor-signaling-potential-role-in-prostate-cancer-therapy
#19
REVIEW
Vito Cucchiara, Joy C Yang, Vincenzo Mirone, Allen C Gao, Michael G Rosenfeld, Christopher P Evans
Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome...
January 16, 2017: Cancers
https://www.readbyqxmd.com/read/28263212/a-phase-1-trial-of-cabazitaxel-combined-with-188-re-hydroxyethylidene-diphosphonate-in-patients-with-metastatic-castration-resistant-prostate-cancer-who-progressed-on-or-after-a-docetaxel-containing-treatment-the-recab-trial
#20
Joyce M van Dodewaard-de Jong, Esther W Bouman-Wammes, Haiko J Bloemendal, Henk M W Verheul, John M H de Klerk, Alfons J M van den Eertwegh
PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as Re-hydroxyethylidene diphosphonate (HEDP), are effective for pain palliation and have a marked antitumor effect. Cabazitaxel is the standard second-line chemotherapy for mCRPC patients. We performed a phase 1 study investigating the safety and feasibility of the combined treatment with Re-HEDP and cabazitaxel in mCRPC patients. METHODS: Patients with mCRPC and documented disease progression on or after docetaxel were eligible for inclusion...
March 3, 2017: Clinical Nuclear Medicine
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