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Castrate resistent

Gaetano Facchini, Carla Cavaliere, Carmine D'Aniello, Gelsomina Iovane, Sabrina Rossetti
In the pre-chemotherapy (CT) and post-CT settings of metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate plus prednisone (AAP) significantly extended median overall survival and radiographic progression-free survival (PFS) compared with prednisone alone. Yet, few data are available on therapy efficacy in the subgroup with visceral metastases, who represent a small population with poor prognosis. The aim of this study was to describe the clinical experience of AAP in patients with mCRPC with liver and/or lung metastases in real-world setting...
October 12, 2018: Anti-cancer Drugs
Niranjan J Sathianathen, Yiannis A Philippou, Gretchen M Kuntz, Badrinath R Konety, Shilpa Gupta, Alastair D Lamb, Philipp Dahm
BACKGROUND: There has been considerable development in the treatment of advanced prostate cancer over the last decade. A number of agents, including docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and sipuleucel-T, have been reported to improve outcomes in men with castration-resistant disease and their use is being explored in hormone-sensitive prostate cancer. OBJECTIVES: To assess the effects of early taxane-based chemohormonal therapy for newly diagnosed, metastatic, hormone-sensitive prostate cancer...
October 15, 2018: Cochrane Database of Systematic Reviews
Bogdan Mitran, Ken Gösta Andersson, Elin Lindström, Javad Garousi, Maria Rosestedt, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova, John Löfblom
The epidermal growth factor receptor (EGFR) is often overexpressed during prostate cancer (PCa) progression towards androgen‑independence after hormone therapy, but the overexpression is lower than in other types of cancers. Despite the low expression, EGFR has emerged as a promising therapeutic target for patients with castration‑resistant PCa. Non‑invasive methods for determination of EGFR expression in PCa can serve for patient stratification and therapy response monitoring. Radionuclide imaging probes based on affibody molecules (7 kDa) provide high contrast imaging of cancer‑associated molecular targets...
October 15, 2018: Oncology Reports
Vincenzo Di Nunno, Lidia Gatto, Matteo Santoni, Alessia Cimadamore, Antonio Lopez-Beltran, Liang Cheng, Marina Scarpelli, Rodolfo Montironi, Francesco Massari
Management of localized and advanced prostate cancer benefits from several therapeutic options with a surprising improvement in terms of clinical outcome. The selection of patients more likely to benefit from a specific approach still remains a key issue as well as the early identification of patients with aggressive disease which could benefit from a more aggressive treatment strategy. The lack of reliable bio-marker in castration resistant setting able to monitor response to treatment and early inform about tumor progression is an emerging issue...
2018: Frontiers in Oncology
Fernando Vázquez-Alonso, Ignacio Puche-Sanz, José Manuel Cózar-Olmo
OBJECTIVES: There is no broad consensus about what diagnostic tests use for CRPC follow up as well as their frequency. Our objective is to review and analyze the most important CRPC follow up patterns described in the literature to date. METHODS: We performed a critical analysis of the recommendations for follow up most universally employed (PCWG3, RADAR, St Gallen consensus, NCCN guidelines, EAU guidelines) RESULTS: CT scan and bone scan are the routine recommended diagnostic tests, in front of other techniques such as PET/CT or MRI, that may improve the diagnostic efficacy but they have the problem of availability and lack of internal validity for follow up...
September 2018: Archivos Españoles de Urología
Cristina Quicios-Dorado, Eduardo Bolufer-Moragues, Carmen Gomis-Goti, Ramiro Cabello-Benavente, Pablo Javier Cannata-Ortiz, Carmen González-Enguita
Castration resistant prostate cancer (CRPC) is characterized by an important molecular, pathological and clinical heterogeneity. Although most of them present androgen receptor (AR) signal dependence, there are independent phenotypes. Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype with adverse prognosis due to late diagnosis, heterogeneous clinical features and lack of effective systemic treatments. Platinum based chemotherapy is the standard treatment, presenting short limited responses...
September 2018: Archivos Españoles de Urología
Ana Victoria Ojeda, María José Ledo, José Luís Alvarez-Ossorio
Prostate Cancer is the second most frequent malignant neoplasm in males in the world. At the end of the disease, when the tumor becomes resistant to castration, we have a wide range of treatment possibilities aimed at the Androgenic Receptor, androgens synthesis, the skeleton, chemotherapy, and even new molecular targets that are still under investigation. Today, the best sequence of treatment for each patient has not been established yet. OBJECTIVE: The objective of this work is to review the current scene of treatment in castrate resistant prostate cancer, as well as the latest developments and strategies to choose the best sequence in each patient...
September 2018: Archivos Españoles de Urología
Juan Ignacio Pascual Piédrola, Mateo Hevia Suárez, Francisco Javier Ancizu Markert, Angel García Cortés, Pablo Doménech López, Santiago Chiva San Román, José María Velis Campillo, Fernando Díez-Caballero Alonso, José Enrique Robles García, David Rosell Costa, Felipe Villacampa Aubá, Fernando Ramón de Fata Chillón, Bernardino Miñana López
Prostate cancer is a health problem in many Countries worldwide. Understanding the essential function of androgens in the prostate physiology led to the development of hormonal blockade as a therapeutic option in advanced disease, with limited response with time and development of resistance. In this stage, where castration resistant prostate cancer (CRPC) is defined, it is associated with poor prognosis because survival varies between 18 and 24 months. Even with castration levels, tumors are dependent on the functional androgen receptor (AR)...
September 2018: Archivos Españoles de Urología
Ana Loizaga-Iriarte, Isabel Camargo Ibargarai, Nerea Senarriaga-Ruiz de la Illa, Isabel Lacasa-Viscasillas, Miguel Unda-Urzaiz
OBJECTIVE: To analyze the available evidence on Radium 223 therapy, an alfa particle emitter with specific action on bone metastases, studied on patients with castration resistant prostate cancer. EVIDENCE ACQUISITION: We review the pivotal study ALSYMPCA, that served to get the drug approval for this phase of the disease, and the new data obtained from its use. We also performed a search of ongoing studies with Radium 223 alone or in combination with other molecules...
September 2018: Archivos Españoles de Urología
Bernardino Miñana López, Felipe Villacampa Aubá, Fernando Ramón de Fata Chillón, Francisco Javier Ancizu Markert, Angel García Cortés, Pablo Doménech López, Santiago Chiva San Román, José María Velis Campillo, Fernando Díez-Caballero Alonso, José Enrique Robles García, David Rosell Costa, Juan Ignacio Pascual Piédrola
We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity...
September 2018: Archivos Españoles de Urología
Antonio Rosino, Inmaculada Ballester, Julián Tudela, Enrique González-Billalabeitia
Prostate cancer is the second mortality cause among males with cancer. Patients with metastatic castration resistant prostate cancer (mCRPC) essentially die due to tumor progression in a castration resistance situation. Docetaxel based chemotherapy was the first therapeutic strategy that demonstrated a survival increase, in addition to pain decrease, increase in tumor responses and quality of life benefit, and it currently continues being useful after the incorporation of new therapies for the treatment of mCRPC...
September 2018: Archivos Españoles de Urología
Emilio Ríos González, Luis Martínez-Piñeiro
Androgen deprivation therapy is part of the initial treatment of patients with metastatic prostate cancer. Nevertheless, after an initial response and despite maintaining an effective testosterone suppression, the tumor is able to continue growing.Enzalutamide is an oral second generation pure antiandrogen that acts at various levels in the signal activation cascade of the androgen receptor and has demonstrated being effective in this phase of the disease. In the clinical trials completed, it has demonstrated benefits in overall patient survival in patients with the diagnosis of metastatic castration resistant prostate cancer...
September 2018: Archivos Españoles de Urología
Alvaro Juárez Soto, Rocío Caballero Cobos, Ruben Campanario Pérez, Rocío Saiz Marenco, Mercedes Herrera Torres, Rafael Gamaza Martínez, Javier Amores Bermúdez
OBJECTIVES: Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its change to the castration resistance state. Recently, new molecules have been developed that significantly increase survival and quality of life of these patients. Abiraterone acetate in combination with prednisone is the first oral hormone therapy that contributed to this change in the approach of the disease. METHODS: Systematic bibliographic review about abiraterone in the treatment of metastatic castration resistant prostate cancer (CPRC), with data on efficacy, safety and quality of life...
September 2018: Archivos Españoles de Urología
Rafael Antonio Medina-López, Miquel Tarón, Ignacio Osman-García, Ignacio Duran
OBJECTIVES: Castration resistant prostate cancer (CRPC) is an heterogeneous disease the molecular basis of which we are starting to know in depth. Currently, there are various pathways and targets under study, and probably many others to be characterized. In this paper, we review the most recent knowledge concerning the molecular biology of CRPC with a special focus on the therapeutic application of this knowledge. METHODS: We performed a bibliographic review using PUBMED as the search engine, including the following terms: "Castration resistant prostate cancer", "genomics", "molecular biology", "AR", "WNT", "mTOR", "PTEN", "cell-cycle", "DNA damage repair gene"and "chromatin modifier genes"...
September 2018: Archivos Españoles de Urología
Sara Martínez-Breijo, Venancio Chantada-Abal, Marcos Aller-Rodríguez, Manuel Bohórquez-Cruz, Felipe Sacristán-Lista, Jose Ponce-Díaz, Darío Vázquez-Martul, Leticia Lamas-Díaz
The androgen-signaling axis plays a pivotal role in the pathogenesis of prostate cancer. Since the landmark discovery by Huggins and Hodges, gonadal depletion of androgens has remained a mainstay of therapy for advanced disease. However, invariably progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression...
September 2018: Archivos Españoles de Urología
B Miñana López
No abstract text is available yet for this article.
September 2018: Archivos Españoles de Urología
Rachael McCool, Kelly Fleetwood, Julie Glanville, Mick Arber, Howard Goodall, Shevani Naidoo
OBJECTIVES: To estimate the relative effectiveness of enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer by conducting a systematic literature review and a network meta-analysis (NMA). METHODS: A systematic literature review identified randomized controlled trials comparing enzalutamide, abiraterone/prednisone, radium-223, sipuleucel-T, or docetaxel with each other or placebo in chemotherapy-naive or mixed populations (with and without prior chemotherapy) with asymptomatic/mildly symptomatic metastatic castration-resistant prostate cancer...
October 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Nitya V Sharma, Kathryn L Pellegrini, Veronique Ouellet, Felipe O Giuste, Selvi Ramalingam, Kenneth Watanabe, Eloise Adam-Granger, Lucresse Fossouo, Sungyong You, Michael R Freeman, Paula Vertino, Karen Conneely, Adeboye O Osunkoya, Dominique Trudel, Anne-Marie Mes-Masson, John A Petros, Fred Saad, Carlos S Moreno
BACKGROUND: Patients with locally advanced or recurrent prostate cancer typically undergo androgen deprivation therapy (ADT), but the benefits are often short-lived and the responses variable. ADT failure results in castration-resistant prostate cancer (CRPC), which inevitably leads to metastasis. We hypothesized that differences in tumor transcriptional programs may reflect differential responses to ADT and subsequent metastasis. RESULTS: We performed whole transcriptome analysis of 20 patient-matched Pre-ADT biopsies and 20 Post-ADT prostatectomy specimens, and identified two subgroups of patients (high impact and low impact groups) that exhibited distinct transcriptional changes in response to ADT...
October 11, 2018: Cancers
Wei-Yu Chen, Tao Zeng, Yu-Chng Wen, Hsiu-Lien Yeh, Kuo-Ching Jiang, Wei-Hao Chen, Qingfu Zhang, Jiaoti Huang, Yen-Nien Liu
Androgen receptor (AR) targeting is an important therapeutic strategy for treating prostate cancer. Most tumors progress to castration-resistant prostate cancer (CRPC) and develop the neuroendocrine (NE) phenotype under androgen deprivation therapy (ADT). The molecular basis for NE transdifferentiation after ADT remains incompletely understood. Herein, we show that an immunocyte expression protein, ZBTB46, induces inflammatory response gene expression and contributes to NE differentiation of prostate cancer cells...
October 9, 2018: Cancer Letters
Young A Yoo, Rajita Vatapalli, Barbara Lysy, Hanlin Mok, Mohamed M Desouki, Sarki A Abdulkadir
Background: Recurrence following androgen-deprivation therapy is associated with adverse clinical outcomes in prostate cancer, but the cellular origins and molecular mechanisms underlying this process are poorly defined. We previously identified a population of castration-resistant luminal progenitor cells expressing Bmi1 in the normal mouse prostate that can serve as a cancer cell-of-origin. Here, we investigate the potential of Bmi1-expressing tumor cells that survive castration to initiate recurrence in vivo...
October 11, 2018: Journal of the National Cancer Institute
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