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Castration-resistant prostate cancer

Antoine Thiery-Vuillemin, Mads Hvid Poulsen, Edouard Lagneau, Guillaume Ploussard, Alison Birtle, Louis-Marie Dourthe, Dominique Beal-Ardisson, Elias Pintus, Redas Trepiakas, Laurent Antoni, Martin Lukac, Suzy Van Sanden, Geneviève Pissart, Alison Reid
Introduction: Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are commonly prescribed for metastatic castration-resistant prostate cancer (mCRPC). Data comparing their effects on patient-reported outcomes (PROs) from routine clinical practice are limited. Methods: AQUARiUS (NCT02813408) is an ongoing, two-cohort, prospective, observational, non-randomised, multicentre, phase IV European study assessing the effects of AAP and ENZ on PROs in 211 patients with mCRPC over 12 months...
2018: ESMO Open
Stefan Aufderklamm, Jörg Hennenlotter, Phillip Leidenberger, Steffen Rausch, Andrea Hohneder, Ursula Kühs, Moritz Maas, Christian Schwentner, Jens Bedke, Arnulf Stenzl, Tilman Todenhöfer
Purpose: Dickkopf-1 (DKK-1) and sclerostin seem to inhibit osteoblast activity by blocking the Wnt pathway, which leads to progression of metastatic prostate cancer (PC). However, it is unknown whether serum levels of these proteins are altered in PC patients with or without metastasis. The aim of this study was to assess DKK-1 and sclerostin serum levels in PC patients, including patients with bone metastases. Methods: The study cohort ( N = 143) consisted of 53 controls with benign prostatic hyperplasia (BPH), 43 with localized PC (PC cM0), and 47 had PC with metastasis (PC cM1)...
2018: Disease Markers
Sigfred Ian R Alpajaro, Jerad A K Harris, Christopher P Evans
BACKGROUND: Non-metastatic castration resistant prostate cancer (M0CRPC) is a heterogenous disease state affecting an estimated 100,000 men in the United States. Development of more sensitive modalities for detection of metastasis has altered the landscape of advanced prostate cancer, but M0CRPC has remained a condition that previously lacked FDA-approved treatment. The emerging data on new generation Androgen Receptor (AR) pathway inhibitors should address this gap in the management of such patients...
August 16, 2018: Prostate Cancer and Prostatic Diseases
Michael T Schweizer, Kathleen Haugk, Jožefa S McKiernan, Roman Gulati, Heather H Cheng, Jessica L Maes, Ruth F Dumpit, Peter S Nelson, Bruce Montgomery, Jeannine S McCune, Stephen R Plymate, Evan Y Yu
[This corrects the article DOI: 10.1371/journal.pone.0198389.].
2018: PloS One
Ashley T Fancher, Yun Hua, Daniel P Camarco, David A Close, Christopher J Strock, Paul A Johnston
Twenty percent of prostate cancer (PCa) patients develop a noncurable drug-resistant form of the disease termed castration-resistant prostate cancer (CRPC). Overexpression of Androgen Receptor (AR) coactivators such as transcriptional intermediary factor 2 (TIF2) is associated with poor CRPC patient outcomes. We describe the implementation of the AR-TIF2 protein-protein interaction biosensor (PPIB) assay in a high-content screening (HCS) campaign of 143,535 compounds. The assay performed robustly and reproducibly and enabled us to identify compounds that inhibited dihydrotestosterone (DHT)-induced AR-TIF2 protein-protein interaction (PPI) formation or disrupted preexisting AR-TIF2 PPIs...
August 15, 2018: Assay and Drug Development Technologies
Brandon Bumbaca, Wei Li
Despite its good initial response and significant survival benefit in patients with castration-resistant prostate cancer (CRPC), taxane therapy inevitably encounters drug resistance in all patients. Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression, and upregulation of efflux transporters...
July 2018: Acta Pharmaceutica Sinica. B
Jillian S Weissenrieder, Jacqueline E Reilly, Jeffrey D Neighbors, Raymond J Hohl
BACKGROUND: Following androgen deprivation for the treatment of advanced adenocarcinoma of the prostate, tumors can progress to neuroendocrine prostate cancer (NEPC). This transdifferentiation process is poorly understood, but trafficking of transcriptional factors and/or cytoskeletal rearrangements may be involved. We observed the role of geranylgeranylation in this process by treatment with digeranyl bisphosphonate (DGBP), a selective inhibitor of geranylgeranyl pyrophosphate synthase which blocks the prenylation of small GTPases such as Rho and Rab family proteins, including Cdc42 and Rac1...
August 14, 2018: Prostate
Qiang Liu, Yunyan Wu, Hiroko Seino, Toshihiro Haga, Tadashi Yoshizawa, Satoko Morohashi, Hiroshi Kijima
Differentiated embryonic chondrocyte (DEC) genes have been reported to be involved in the regulation of mammalian circadian rhythms, differentiation, apoptosis, the response to hypoxia and epithelial‑mesenchymal transition (EMT). Activation of transforming growth factor (TGF)‑β signaling is known to promote EMT for the development of metastatic castration‑resistant prostate cancer (PCa). However, the role of DEC genes in the TGF‑β‑induced EMT of PCa remains unclear. In the present study it was demonstrated that TGF‑β increased the transcriptional/translational levels of DEC1 but decreased those of DEC2 in PC‑3 cells...
August 9, 2018: Molecular Medicine Reports
Jin-Ge Zhao, Jian-Dong Liu, Peng-Fei Shen, Xin Tang, Guang-Xi Sun, Xing-Ming Zhang, Jun-Ru Chen, Kun-Peng Shu, Ming Shi, Hao Zeng
Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly...
August 14, 2018: Asian Journal of Andrology
Joan Carles, Daniel Castellano, María-José Méndez-Vidal, Begoña Mellado, María-Isabel Saez, Aránzazu González Del Alba, José-Luis Perez-Gracia, José Jimenez, Cristina Suárez, Juan M Sepúlveda, Ray Manneh, Ignacio Porras, Cristina López, Rafael Morales-Barrera, José-Ángel Arranz
INTRODUCTION: Although increasing numbers of therapies with proven survival benefits have become available for metastatic castration-resistant prostate cancer (mCRPC), including radium-223, there is still a need for reliable biomarkers that provide information about clinically meaningful outcomes and treatment responses. MATERIALS AND METHODS: This study was a translational study that was conducted prospectively by the Spanish Oncology Genito-Urinary Group and included 45 patients with histologically confirmed mCRPC who were treated with radium-223...
July 21, 2018: Clinical Genitourinary Cancer
Dana E Rathkopf, Howard I Scher
Five new agents have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer, including two targeting androgen receptor signaling (abiraterone acetate plus prednisone; enzalutamide). Recognition that these tumors remain driven by androgen receptor signaling has prompted clinical evaluation of these agents at earlier states in the prostate cancer disease continuum, along with the continued development of new agents targeting this pathway. Areas covered: This article focuses on apalutamide, a next-generation nonsteroidal antiandrogen, with current literature queried in PubMed/Medline...
September 2018: Expert Review of Anticancer Therapy
Tarek A Bismar, Samar Hegazy, Zhaoyong Feng, Darryl Yu, Bryan Donnelly, Nallasivam Palanisamy, Bruce J Trock
OBJECTIVES: To assess the prognostic value of ERG and PTEN protein expression as two of the most common genetic aberration in men with prostate cancer managed non-surgically by androgen deprivation therapy (ADT). MATERIALS AND METHODS: 463 tumor samples were assessed by double immunohistochemistry stains for ERG and PTEN and data correlated with clinical pathological features including, Gleason score, patients' outcome and ADT. RESULTS: ERG expression and PTEN protein loss were present in 28...
August 12, 2018: Journal of Cancer Research and Clinical Oncology
Christina K Cajigas-Du Ross, Shannalee R Martinez, Leanne Woods-Burnham, Alfonso M Durán, Sourav Roy, Anamika Basu, Joshua A Ramirez, Greisha L Ortiz-Hernández, Leslimar Ríos-Colón, Evgeny Chirshev, Evelyn S Sanchez-Hernandez, Ubaldo Soto, Celine Greco, Claude Boucheix, Xin Chen, Juli Unternaehrer, Charles Wang, Carlos A Casiano
Patients with metastatic castration-resistant prostate cancer (mCRPC) develop resistance to conventional therapies including docetaxel (DTX). Identifying molecular pathways underlying DTX resistance is critical for developing novel combinatorial therapies to prevent or reverse this resistance. To identify transcriptomic signatures associated with acquisition of chemoresistance we profiled gene expression in DTX-sensitive and -resistant mCRPC cells using RNA sequencing (RNA-seq). PC3 and DU145 cells were selected for DTX resistance and this phenotype was validated by immunoblotting using DTX resistance markers (e...
July 13, 2018: Oncotarget
Charlotte Fenioux, Christophe Louvet, Emilie Charton, Francois Rozet, Stanislas Ropert, Dominique Prapotnich, Eric Barret, Rafael Sanchez-Salas, Annick Mombet, Nathalie Cathala, Marie-Liesse Joulia, Jean-Luc Molitor, Julie Henriques, Franck Bonnetain, Xavier Cathelineau, Mostefa Bennamoun
OBJECTIVE: To evaluate the effects of switching from Prednisone (P) to Dexamethasone (D) at asymptomatic PSA progression in mCRPC patients treated with Abiraterone-acetate (AA). MATERIAL AND METHODS: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic mCRPC patients, progressing biochemically on AA+P 10mg/d, were included. A corticosteroid-switch to AA+D 0.5mg/d at PSA increase was administered until radiological and/or clinical progression...
August 11, 2018: BJU International
Eric Lu, George V Thomas, Yiyi Chen, Alexander W Wyatt, Paul Lloyd, Jack Youngren, David Quigley, Raymond Bergan, Shawna Bailey, Tomasz M Beer, Felix Y Feng, Eric J Small, Joshi J Alumkal
Background: PARP inhibition is a promising therapeutic strategy for the treatment of men with metastatic castration-resistant prostate cancer whose tumors harbor homologous recombination DNA repair gene alterations. However, questions remain for many practicing clinicians about which patients are ideally suited for PARP inhibitor treatment. This report details our institutional experience using PARP inhibitor therapy in patients whose tumors harbored specific DNA repair gene alterations. Patients and Methods: We performed a retrospective chart review to identify patients at Oregon Health & Science University who were treated with PARP inhibition...
August 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Omar Abdel-Rahman, Winson Y Cheung
BACKGROUND: Local treatment of metastatic prostate cancer and its impact on future disease course requires further assessment. We sought to evaluate the impact of prior local treatment to the prostate on the outcomes of hormone-sensitive prostate cancer (HSPC) patients recruited in the CHAARTED study. PATIENTS AND METHODS: We performed a retrospective analysis of the prospectively collected data among patients with metastatic HSPC in the CHAARTED study, a phase 3 multicenter study conducted between 2006 and 2014...
July 21, 2018: Clinical Genitourinary Cancer
J Carles, A Pichler, H Korunkova, A Tomova, M Ghosn, F El Karak, J Makdessi, I Koroleva, G Barnes, D Bury, A Özatilgan, S Hitier, J Katolicka
OBJECTIVES: To obtain routine clinical practice data on cabazitaxel usage patterns for patients with metastatic castration-resistant prostate cancer (mCRPC) and to describe physician-assessed cabazitaxel effectiveness, health-related quality of life (HRQL) and safety. PATIENTS AND METHODS: CAPRISTANA was an international, observational cohort study examining cabazitaxel use for the treatment of patients with mCRPC. Effectiveness was assessed by overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF) and disease control rate...
August 11, 2018: BJU International
Karen A Cavassani, Rebecca J Meza, David M Habiel, Jie-Fu Chen, Alexander Montes, Manisha Tripathi, Gislâine A Martins, Timothy R Crother, Sungyong You, Cory M Hogaboam, Neil Bhowmick, Edwin M Posadas
BACKGROUND: Recruited myeloid cells are known to promote cancer initiation, malignant progression, metastasis, and resistance to therapy in the tumor niche. We tested the hypothesis that circulating blood monocytes from advanced prostate cancer (PCa) patients exhibit a protumor phenotype and directly influence the tumor microenvironment in response to tumor-derived signals. METHODS: Blood monocytes from advanced and stable PCa patients were cultured, and the conditioned media (CM) were collected and analyzed using standard invasion and wound closure assays to measure effects on invasion and motility of PCa tumor cells...
August 9, 2018: Cancer Medicine
Poorva Bindal, Sharif Aa Jalil, Lisa M Holle, Jessica M Clement
Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma...
August 9, 2018: Journal of Oncology Pharmacy Practice
Jie Zang, Xinrong Fan, Hao Wang, Qingxing Liu, Jingnan Wang, Hui Li, Fang Li, Orit Jacobson, Gang Niu, Zhaohui Zhu, Xiaoyuan Chen
PURPOSE: This translational study is designed to assess the safety, dosimetry and therapeutic response to a single, low-dose of 177 Lu-EB-PSMA-617 in comparison to 177 Lu-PSMA-617 in patients with mCRPC. METHODS: Following institutional review board approval and informed consent, nine patients with mCRPC were recruited. Four patients accepted intravenous injection of 0.80-1.1 GBq (21.5-30 mCi) of 177 Lu-EB-PSMA-617, then underwent serial whole-body planar and SPECT/CT imaging at 2, 24, 72, 120 and 168 h...
August 8, 2018: European Journal of Nuclear Medicine and Molecular Imaging
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