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Castrate resistent

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https://www.readbyqxmd.com/read/30106164/inhibiting-geranylgeranyl-diphosphate-synthesis-reduces-nuclear-androgen-receptor-signaling-and-neuroendocrine-differentiation-in-prostate-cancer-cell-models
#1
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
https://www.readbyqxmd.com/read/30106153/correlation-between-dec1-dec2-and-epithelial%C3%A2-mesenchymal-transition-in-human-prostate-cancer-pc%C3%A2-3-cells
#2
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
https://www.readbyqxmd.com/read/30106011/prior-switching-to-a-second-line-nonsteroidal-antiandrogen-does-not-impact-the-therapeutic-efficacy-of-abiraterone-acetate-in-patients-with-metastatic-castration-resistant-prostate-cancer-a-real-world-retrospective-study
#3
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
https://www.readbyqxmd.com/read/30104161/circulating-tumor-cells-as-a-biomarker-of-survival-and-response-to-radium-223-therapy-experience-in-a-cohort-of-patients-with-metastatic-castration-resistant-prostate-cancer
#4
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
https://www.readbyqxmd.com/read/30101644/apalutamide-for-the-treatment-of-prostate-cancer
#5
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
https://www.readbyqxmd.com/read/30101374/clinical-utility-of-assessing-pten-and-erg-protein-expression-in-prostate-cancer-patients-a-proposed-method-for-risk-stratification
#6
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
https://www.readbyqxmd.com/read/30100995/rna-sequencing-reveals-upregulation-of-a-transcriptomic-program-associated-with-stemness-in-metastatic-prostate-cancer-cells-selected-for-taxane-resistance
#7
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
https://www.readbyqxmd.com/read/30099821/switch-from-abiraterone-prednisone-to-abiraterone-dexamethasone-at-asymptomatic-psa-progression-in-metastatic-castration-resistant-prostate-cancer-mcrpc-patients
#8
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
https://www.readbyqxmd.com/read/30099369/dna-repair-gene-alterations-and-parp-inhibitor-response-in-patients-with-metastatic-castration-resistant-prostate-cancer
#9
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
https://www.readbyqxmd.com/read/30098982/impact-of-prior-local-treatment-on-the-outcomes-of-metastatic-hormone-sensitive-prostate-cancer-secondary-analysis-of-a-randomized-controlled-trial
#10
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
https://www.readbyqxmd.com/read/30098093/observational-multicenter-study-of-cabazitaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-previously-treated-with-docetaxel-capristana
#11
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
https://www.readbyqxmd.com/read/30094958/circulating-monocytes-from-prostate-cancer-patients-promote-invasion-and-motility-of-epithelial-cells
#12
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
https://www.readbyqxmd.com/read/30092742/potential-role-of-rituximab-in-metastatic-castrate-resistant-prostate-cancer
#13
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
https://www.readbyqxmd.com/read/30090965/first-in-human-study-of-177-lu-eb-psma-617-in-patients-with-metastatic-castration-resistant-prostate-cancer
#14
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
https://www.readbyqxmd.com/read/30089652/inhibition-of-cholesterol-biosynthesis-overcomes-enzalutamide-resistance-in-castration-resistant-prostate-cancer-crpc
#15
Yifan Kong, Lijun Cheng, Fengyi Mao, Zhuangzhuang Zhang, Yanquan Zhang, Elia Farah, Jacob Bosler, Yunfeng Bai, Nihal Ahmad, Shihuan Kuang, Lang Li, Xiaoqi Liu
Enzalutamide, a nonsteroidal second-generation antiandrogen, has been recently approved for the management of castration-resistant prostate cancer (CRPC). Although patients can benefit from enzalutamide at the beginning of this therapy, acquired enzalutamide resistance usually occurs within a short period. This motivated us to investigate the mechanism involved and possible approaches for overcoming enzalutamide resistance in CRPC. In the present study, we found that HMG-CoA reductase (HMGCR), a crucial enzyme in the mevalonate pathway for sterol biosynthesis, is elevated in enzalutamide-resistant prostate cancer cell lines...
August 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30086276/castration-resistant-prostate-cancer-aua-guideline-amendment-2018
#16
William T Lowrance, Mohammad Hassan Murad, William K Oh, David F Jarrard, Matthew J Resnick, Michael S Cookson
PURPOSE: The purpose of this amendment is to incorporate newly-published literature to provide a rational basis for the management of patients with non-metastatic castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: The original systematic review and meta-analysis of the published literature yielded 303 studies published from 1996 through 2013. This review informed the majority of the guideline statements from the 2013 guideline. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence...
August 4, 2018: Journal of Urology
https://www.readbyqxmd.com/read/30084431/prognostic-role-of-chromogranin-a-in-castration-resistant-prostate-cancer-a-meta-analysis
#17
Peng Hong, Run-Qi Guo, Gang Song, Kai-Wei Yang, Lei Zhang, Xue-Song Li, Kai Zhang, Li-Qun Zhou
We aimed to investigate the prognostic value of chromogranin A (CgA) in castration-resistant prostate cancer (CRPC). We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows: progression-free survival (PFS) was associated with CgA level (hazard ratio [HR] = 2...
July 31, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/30084412/polymorphisms-in-cytotoxic-t-lymphocyte-associated-antigen-4-gene-does-not-affect-scytotoxic-t-lymphocyte-associated-antigen-4-levels-in-human-papillomavirus-infected-women-with-or-without-cervical-cancer
#18
Priyanka Wagh, Priyanka Kulkarni, Shilpa Kerkar, Himangi Warke, Hemangi Chaudhari, Kedar Deodhar, Bharat Rekhi, Hemant Tongaonkar, Jayanti Mania-Pramanik
Background: Cervical cancer (CaCx) is the second most common cancer in Indian women. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) + 49 AA polymorphism is known to be associated with CaCx. Current attempt is to use immunotherapy for the treatment of metastatic melanoma and metastatic castration-resistant prostate cancer, i.e., blocking of CTLA-4 using a fully human monoclonal CTLA-4 antibody to disrupt its inhibitory signal. This allows the CTLs to destroy the cancer cells. There is no information available on the soluble level of CTLA-4 on which the immunotherapy is targeted...
April 2018: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/30083962/phase-ii-randomized-double-blind-placebo-controlled-study-of-tivantinib-in-men-with-asymptomatic-or-minimally-symptomatic-metastatic-castration-resistant-prostate-cancer-mcrpc
#19
Paul Monk, Glenn Liu, Walter M Stadler, Susan Geyer, Ying Huang, John Wright, Miguel Villalona-Calero, James Wade, Russell Szmulewitz, Shilpa Gupta, Amir Mortazavi, Robert Dreicer, Roberto Pili, Nancy Dawson, Saby George, Jorge A Garcia
Background Tivantinib is a non-ATP competitive inhibitor of c-MET receptor tyrosine kinase that may have additional cytotoxic mechanisms including tubulin inhibition. Prostate cancer demonstrates higher c-MET expression as the disease progresses to more advanced stages and to a castration resistant state. Methods 80 patients (pts) with asymptomatic or minimally symptomatic mCRPC were assigned (2:1) to either tivantinib 360 mg PO BID or placebo (P). The primary endpoint was progression free survival (PFS). Results Of the 80 pts...
August 7, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/30083960/current-status-of-androgen-receptor-splice-variant-7-inhibitor-niclosamide-in-castrate-resistant-prostate-cancer
#20
REVIEW
Navid Sobhani, Daniele Generali, Alberto D'Angelo, Michele Aieta, Giandomenico Roviello
Castrate-Resistant Prostate-Cancer (CRPC) is one of the most common malignancies occurring in men. Unfortunately, even if several recently approved agents clinically improved the outcome of CRPC patients, none of these is curative especially for a splice version of the Androgen Receptor (AR) AR-V7, which is a variant of the receptor constitutively activated and does not require the presence of androgens for the activation AR down-stream pathways. Since high AR-V7 expression is one of the most common features of CRPC, targeting this receptor variant is considered as one of the most promising strategies for treating this disease...
August 7, 2018: Investigational New Drugs
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