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Metastatic prostatic cancer clinical treatment

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https://www.readbyqxmd.com/read/28228262/targeting-dna-damage-response-in-prostate-cancer-by-inhibiting-androgen-receptor-cdc6-atr-chk1-signaling
#1
Styliani Karanika, Theodoros Karantanos, Likun Li, Jianxiang Wang, Sanghee Park, Guang Yang, Xuemei Zuo, Jian H Song, Sankar N Maity, Ganiraju C Manyam, Bradley Broom, Ana M Aparicio, Gary E Gallick, Patricia Troncoso, Paul G Corn, Nora Navone, Wei Zhang, Shuhua Li, Timothy C Thompson
Cell division cycle 6 (CDC6), an androgen receptor (AR) target gene, is implicated in regulating DNA replication and checkpoint mechanisms. CDC6 expression is increased during prostate cancer (PCa) progression and positively correlates with AR in PCa tissues. AR or CDC6 knockdown, together with AZD7762, a Chk1/2 inhibitor, results in decreased TopBP1-ATR-Chk1 signaling and markedly increased ataxia-telangiectasia-mutated (ATM) phosphorylation, a biomarker of DNA damage, and synergistically increases treatment efficacy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28223166/efficacy-of-photochemical-internalisation-using-disulfonated-chlorin-and-porphyrin-photosensitisers-an-in-vitro-study-in-2d-and-3d-prostate-cancer-models
#2
Alejandra Martinez de Pinillos Bayona, Josephine H Woodhams, Hayley Pye, Rifat A Hamoudi, Caroline M Moore, Alexander J MacRobert
This study shows the therapeutic outcome of Photochemical Internalisation (PCI) in prostate cancer in vitro surpasses that of Photodynamic Therapy (PDT) and could improve prostate PDT in the clinic, whilst avoiding chemotherapeutics side effects. In addition, the study assesses the potential of PCI with two different photosensitisers (TPCS2a and TPPS2a) in prostate cancer cells (human PC3 and rat MatLyLu) using standard 2D monolayer culture and 3D biomimetic model. Photosensitisers were used alone for photodynamic therapy (PDT) or with the cytotoxin saporin (PCI)...
February 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28213364/safety-and-antitumor-activity-of-apalutamide-arn-509-in-metastatic-castration-resistant-prostate-cancer-with-and-without-prior-abiraterone-acetate-and-prednisone
#3
Dana E Rathkopf, Emmanuel S Antonarakis, Neal D Shore, Ronald F Tutrone, Joshi J Alumkal, Charles J Ryan, Mansoor Saleh, Ralph J Hauke, Rajesh Bandekar, Edna Chow Maneval, Carla J de Boer, Margaret K Yu, Howard I Scher
PURPOSE: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). EXPERIMENTAL DESIGN: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28209912/detection-efficacy-of-hybrid-68-ga-psma-ligand-pet-ct-in-prostate-cancer-patients-with-biochemical-recurrence-after-primary-radiation-therapy-defined-by-phoenix-criteria
#4
Ingo Einspieler, Isabel Rauscher, Charlotte Düwel, Markus Krönke, Christoph Rischpler, Gregor Habl, Sabrina Dewes, Armin Ott, Hans-Jürgen Wester, Markus Schwaiger, Tobias Maurer, Matthias Eiber
The aim of this retrospective study was to evaluate the detection rate of Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA ligand) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrent prostate cancer (PC) defined by Phoenix criteria after external beam radiotherapy (EBRT) or brachytherapy as primary treatment. Methods: 118 patients were finally eligible for this retrospective analysis with a median prostate-specific antigen (PSA) of 6.4 ng/mL (range: 2.2-158...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28208703/androgen-receptor-signaling-in-salivary-gland-cancer
#5
REVIEW
Martin G Dalin, Philip A Watson, Alan L Ho, Luc G T Morris
Salivary gland cancers comprise a small subset of human malignancies, and are classified into multiple subtypes that exhibit diverse histology, molecular biology and clinical presentation. Local disease is potentially curable with surgery, which may be combined with adjuvant radiotherapy. However, metastatic or unresectable tumors rarely respond to chemotherapy and carry a poorer prognosis. Recent molecular studies have shown evidence of androgen receptor signaling in several types of salivary gland cancer, mainly salivary duct carcinoma...
February 8, 2017: Cancers
https://www.readbyqxmd.com/read/28208611/betulinic-acid-mediated-apoptosis-in-human-prostate-cancer-cells-involves-p53-and-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathways
#6
Eswar Shankar, Ailin Zhang, Daniel Franco, Sanjay Gupta
Defects in p53 and nuclear factor-kappa B (NF-κB) signaling pathways are frequently observed in the initiation and development of various human malignancies, including prostate cancer. Clinical studies demonstrate higher expression of NF-κB/p65/RelA, NF-κB/p50/RelB, and cRel as well as downregulation of the p53 network in primary prostate cancer specimens and in metastatic tumors. Betulinic acid (BA), is a triterpenoid that has been reported to be an effective inducer of apoptosis through modification of several signaling pathways...
February 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28199075/first-brazilian-consensus-of-advanced-prostate-cancer-recommendations-for-clinical-practice
#7
Andre Deeke Sasse, Evanius Garcia Wiermann, Daniel Herchenhorn, Diogo Assed Bastos, Fabio A Schutz, Fernando Cotait Maluf, George Coura, Igor Alexandre Protzner Morbeck, Juliano J Cerci, Oren Smaletz, Volney Soares Lima, Ari Adamy, Franz Santos de Campos, Gustavo Franco Carvalhal, Leandro Casemiro Cezar, Marcos Francisco Dall'Oglio, Marcus Vinicius Sadi, Rodolfo Borges Dos Reis, Lucas Nogueira
INTRODUCTION: Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. OBJECTIVES: This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology...
February 16, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28190749/role-of-radical-prostatectomy-in-metastatic-prostate-cancer-a-review
#8
REVIEW
Michael J Metcalfe, Marc C Smaldone, Daniel W Lin, Ana M Aparicio, Brian F Chapin
CONTEXT: Recent demonstration of efficacy with the use of chemohormonal therapy for men with metastatic prostate cancer (mPCa) has expanded the therapeutic options for these patients. Furthermore, multimodal therapy to treat systemic disease in the context of locoregional control has gained increasing interest. Concomitantly, the role of radical prostatectomy (RP) in multimodal treatment for locally advanced prostate cancer is expanding. As a result, there is interest in investigating the potential benefit of cytoreductive RP in mPCa...
February 9, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28174422/antarlides-f-h-new-members-of-the-antarlide-family-produced-by-streptomyces-sp-bb47
#9
Shun Saito, Takahiro Fujimaki, Watanalai Panbangred, Ryuichi Sawa, Yasuhiro Igarashi, Masaya Imoto
Castration-resistant prostate cancer (CRPC) is the most aggressive form of this disease. CRPC remains dependent on androgen receptor (AR) signaling. Therefore, a novel AR antagonist, enzalutamide, is used clinically for the treatment of men with metastatic CRPC. However, enzalutamide-resistant AR has appeared, and a new type of AR antagonist is desired. Previously, in the course of screening for a new type of AR antagonist, we isolated a series of compounds, designated antarlides A-E, that share a novel 22-membered-ring macrocyclic structure and are produced by Streptomyces sp...
February 8, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28171710/clinical-outcomes-and-survival-surrogacy-studies-of-prostate-specific-antigen-declines-following-enzalutamide-in-men-with-metastatic-castration-resistant-prostate-cancer-previously-treated-with-docetaxel
#10
Andrew J Armstrong, Fred Saad, De Phung, Carl Dmuchowski, Neal D Shore, Karim Fizazi, Mohammad Hirmand, David Forer, Howard I Scher, Johann De Bono
BACKGROUND: In the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate-specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting. METHODS: Men in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment...
February 7, 2017: Cancer
https://www.readbyqxmd.com/read/28169118/bone-health-and-bone-targeted-therapies-for-prostate-cancer-a-programme-in-evidence-based-care-cancer-care-ontario-clinical-practice-guideline
#11
S M H Alibhai, K Zukotynski, C Walker-Dilks, U Emmenegger, A Finelli, S C Morgan, S J Hotte, E Winquist
AIMS: To make recommendations with respect to bone health and bone-targeted therapies in men with prostate cancer. MATERIALS AND METHODS: A systematic review was carried out by searching MEDLINE, EMBASE and the Cochrane Library from inception to January 2016. Systematic reviews and randomised-controlled trials were considered for inclusion if they involved therapies directed at improving bone health or outcomes such as skeletal-related events, pain and quality of life in patients with prostate cancer either with or without metastases to bone...
February 3, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28161323/a-multicenter-phase-i-study-of-cabazitaxel-mitoxantrone-and-prednisone-for-chemotherapy-na%C3%A3-ve-patients-with-metastatic-castration-resistant-prostate-cancer-a-department-of-defense-prostate-cancer-clinical-trials-consortium-study
#12
Rahul Aggarwal, Alan Bryce, Charles J Ryan, Andrea Harzstark, Christina Derleth, Won Kim, Terence Friedlander, Amy M Lin, Tammy Rodvelt-Bagchi, Mallika Dhawan, Li Zhang, Mina Lee, Eric Siebeneck, Jeffrey Hough, Eric J Small
BACKGROUND: Cabazitaxel plus prednisone has significant activity in patients with chemotherapy-naïve and pretreated metastatic castration-resistant prostate cancer (mCRPC). Mitoxantrone has antitumor activity in mCRPC and nonoverlapping mechanism of action and toxicity profile. OBJECTIVE: To establish the maximally tolerated dose of the combination of cabazitaxel, mitoxantrone, and prednisone. METHODS AND MATERIALS: Patients with chemotherapy-naïve mCRPC were prospectively enrolled in a multicenter phase 1 trial...
February 1, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28159490/chemohormonal-therapy-in-metastatic-hormone-sensitive-prostate-cancer-sweeney-cj-chen-yh-carducci-m-liu-g-jarrard-df-eisenberger-m-wong-yn-hahn-n-kohli-m-cooney-mm-dreicer-r-vogelzang-nj-picus-j-shevrin-d-hussain-m-garcia-ja-dipaola-rs-department-of-medicine
#13
Eggener Scott
BACKGROUND: Androgen deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. METHODS: We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75mg per square meter of body-surface area every 3wk for 6 cycles) or ADT alone...
March 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28156002/lucap-prostate-cancer-patient-derived-xenografts-reflect-the-molecular-heterogeneity-of-advanced-disease-an-d-serve-as-models-for-evaluating-cancer-therapeutics
#14
Holly M Nguyen, Robert L Vessella, Colm Morrissey, Lisha G Brown, Ilsa M Coleman, Celestia S Higano, Elahe A Mostaghel, Xiaotun Zhang, Lawrence D True, Hung-Ming Lam, Martine Roudier, Paul H Lange, Peter S Nelson, Eva Corey
BACKGROUND: Metastatic prostate cancer is a common and lethal disease for which there are no therapies that produce cures or long-term durable remissions. Clinically relevant preclinical models are needed to increase our understanding of biology of this malignancy and to evaluate new agents that might provide effective treatment. Our objective was to establish and characterize patient-derived xenografts (PDXs) from advanced prostate cancer (PC) for investigation of biology and evaluation of new treatment modalities...
February 3, 2017: Prostate
https://www.readbyqxmd.com/read/28152876/choosing-wisely-in-oncology-screening-for-a-new-primary-cancer-in-patients-with-metastatic-disease
#15
Lorraine Lipscombe, Hadas Fischer, Jill Tinmouth, Peter Austin, Kinwah Fung, Matthew C Cheung
: 295 Background: The Choosing Wisely Canada (CWC) campaign aims to start conversations about unnecessary treatments and procedures in order to improve quality of care. In particular, the CWC campaign in cancer seeks to reduce interventions that are not supported by evidence and contribute to unnecessary rising costs of cancer care. We sought to document the performance of cancer screening for a new primary cancer in patients with existing metastatic cancer (CWC statement #2). METHODS: We used population-based administrative health care databases from Ontario, Canada held at the Institute for Clinical Evaluative Sciences (ICES)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28151974/assessment-of-a-prognostic-model-psa-metrics-and-toxicities-in-metastatic-castrate-resistant-prostate-cancer-using-data-from-project-data-sphere-pds
#16
Bethany Pitcher, Leila Khoja, Robert J Hamilton, Kald Abdallah, Melania Pintilie, Anthony M Joshua
BACKGROUND: Prognostic models in metastatic castrate resistant prostate cancer (mCRPC) may have clinical utility. Using data from PDS, we aimed to 1) validate a contemporary prognostic model (Templeton et al., 2014) 2) evaluate prognostic impact of concomitant medications and PSA decrease 3) evaluate factors associated with docetaxel toxicity. METHODS: We accessed data on 2,449 mCRPC patients in PDS. The existing model was validated with a continuous risk score, time-dependent receiver operating characteristic (ROC) curves, and corresponding time-dependent Area under the Curve (tAUC)...
2017: PloS One
https://www.readbyqxmd.com/read/28147927/a-case-report-of-enzalutamide-administration-in-a-dialysis-dependent-patient-with-castration-resistant-prostate-cancer
#17
Erica S Tsang, Marie de Haan, Bernhard J Eigl
Enzalutamide, an androgen receptor signaling inhibitor, is a standard of care treatment for metastatic castration-resistant prostate cancer. We present the first reported case of enzalutamide in a patient with end-stage renal disease, on dialysis. While there were no significant toxicities, a sustained increase in systolic blood pressure was maintained after starting enzalutamide, suggestive of a degree of drug accumulation. Further evaluation of novel hormonal agents in end-stage renal disease patients should be encouraged as this population is typically excluded from clinical trials...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28144789/procaid-a-phase-i-clinical-trial-to-combine-the-akt-inhibitor-azd5363-with-docetaxel-and-prednisolone-chemotherapy-for-metastatic-castration-resistant-prostate-cancer
#18
Simon J Crabb, Alison J Birtle, Karen Martin, Nichola Downs, Ian Ratcliffe, Tom Maishman, Mary Ellis, Gareth Griffiths, Stuart Thompson, Lidia Ksiazek, Vincent Khoo, Robert J Jones
Background Docetaxel and prednisolone chemotherapy (DP) extends survival in metastatic castration resistant prostate cancer (mCRPC). However, emergent clinical resistance is almost inevitable. AKT pathway activation is highly prevalent in mCRPC contributing to disease progression and DP resistance. AZD5363 is a potent oral pan-AKT inhibitor with pre-clinical data indicating activity in mCRPC and synergy with docetaxel. Methods This phase I trial was to determine an AZD5363 recommended phase II dose (RP2D) for combination with DP...
February 1, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28142149/cancer-stem-cells-in-prostate-cancer-implications-for-targeted-therapy
#19
Ricardo Leão, Célia Domingos, Arnaldo Figueiredo, Robert Hamilton, Uri Tabori, Pedro Castelo-Branco
Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies include surgery, radiation, hormonal ablation, and chemotherapy. Despite increasing efforts, these therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. The cancer stem cell (CSC) hypothesis is an emerging model that explains many of the molecular characteristics of oncological disease as well as the tendency of cancers to relapse, metastasize, and develop resistance to conventional therapies...
February 1, 2017: Urologia Internationalis
https://www.readbyqxmd.com/read/28141932/an-expanded-portfolio-of-survival-metrics-for-assessing-anticancer-agents
#20
Jennifer Karweit, Srividya Kotapati, Samuel Wagner, James W Shaw, Steffan W Wolfe, Amy P Abernethy
OBJECTIVES: With the introduction of more effective anticancer agents that prolong survival, there is a need for new methods to define the clinical value of treatments. The objective of this preliminary qualitative and quantitative analysis was to assess the utility of an expanded portfolio of survival metrics to differentiate the value of anticancer agents. STUDY DESIGN: A literature review was conducted of phase 3 trial data, reported in regulatory submissions within the last 10 years of agents for 6 metastatic cancers (breast cancer, colorectal cancer [CRC], melanoma, non-small cell lung cancer [NSCLC], prostate cancer [PC], and renal cell cancer [RCC])...
January 2017: American Journal of Managed Care
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