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Enzalutamide resistance

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https://www.readbyqxmd.com/read/29340160/stereotactic-body-radiation-therapy-for-the-treatment-of-oligoprogression-on-androgen-receptor-targeted-therapy-in-castration-resistant-prostate-cancer
#1
Thu-Cuc Nguyen, Ravneet Bajwa, Shahla Bari, Azka Ali, William Paul Skelton, Roland-Austin Federico, Rohit Bishnoi, Justin W Wray, Robert A Zlotecki, Long H Dang, Jameel Muzaffar
Castration-resistant prostate cancer is an incurable disease. To date, six agents-abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T- have shown clinical efficacy in phase III clinical trials, leading to their FDA approval. Patients are typically sequenced through most or all of these agents, and then eventually succumb to their disease. Development of new treatments remains an unmet need. We report a case of a patient who progressed on enzalutamide with a single enlarging metastatic lesion, was treated with ablative stereotactic body radiation therapy while maintaining the same systemic treatment, who then had durable complete remission...
January 2018: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29340039/integrative-molecular-network-analysis-identifies-emergent-enzalutamide-resistance-mechanisms-in-prostate-cancer
#2
Carly J King, Josha Woodward, Jacob Schwartzman, Daniel J Coleman, Robert Lisac, Nicholas J Wang, Kathryn Van Hook, Lina Gao, Joshua Urrutia, Mark A Dane, Laura M Heiser, Joshi J Alumkal
Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339044/the-cardiovascular-toxicity-of-abiraterone-and-enzalutamide-in-prostate-cancer
#3
Roberto Iacovelli, Chiara Ciccarese, Emilio Bria, Mario Romano, Emanuela Fantinel, Davide Bimbatti, Alessandro Muraglia, Antonio Benito Porcaro, Salvatore Siracusano, Matteo Brunelli, Renzo Mazzarotto, Walter Artibani, Giampaolo Tortora
INTRODUCTION: The cardiovascular toxicity related to abiraterone and enzalutamide has been previously studied by our group. In this analysis, we aim to update our previous findings related to abiraterone and enzalutamide, including the new available evidence, both in castration-resistant and hormone-sensitive prostate cancer. PATIENTS AND METHODS: Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29332354/inhibition-of-telomerase-potentiates-enzalutamide-efficiency-of-androgen-sensitive-human-prostate-cancer-cells
#4
Karaca Kaan Gecgel, Mustafa Muduroglu, Suat Erdogan
PURPOSE: Androgen deprivation therapy (ADT) is one of the main strategies to treat prostate cancer (PCa) at various stages of its development. Androgen receptor (AR) antagonists such as enzalutamide are mainstay treatments for castration-sensitive prostate cancer. Though, a majority of patients initially respond to ADT, most will eventually progress to castrate-resistant, due to the development of different mutations on the AR. PCa cells express high telomerase activity, and there is a correlation between the total activity of telomerase and the Gleason score...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331381/clinical-outcomes-of-first-line-abiraterone-acetate-or-enzalutamide-for-metastatic-castration-resistant-prostate-cancer-after-androgen-deprivation-therapy%C3%A2-docetaxel-or-adt-alone-for-metastatic-hormone-sensitive-prostate-cancer
#5
Edoardo Francini, Steven Yip, Shubidito Ahmed, Haocheng Li, Luke Ardolino, Carolyn P Evan, Marina Kaymakcalan, Grace K Shaw, Philip W Kantoff, Mary-Ellen Taplin, Nimira S Alimohamed, Anthony M Joshua, Daniel Y C Heng, Christopher J Sweeney
BACKGROUND: The CHAARTED (ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) and STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trials showed that the addition of docetaxel (D) to androgen deprivation therapy (ADT) prolonged longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of upfront D on subsequent therapies is still unexplored. As abiraterone acetate (AA) and enzalutamide (E) are the most commonly used first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), we aimed to assess whether they maintained their efficacy after ADT+D versus ADT alone...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29326358/targeted-alpha-therapy-of-mcrpc-with-225actinium-psma-617-swimmer-plot-analysis-suggests-efficacy-regarding-duration-of-tumor-control
#6
Clemens Kratochwil, Frank Bruchertseifer, Hendrik Rathke, Markus Hohenfellner, Frederik L Giesel, Uwe Haberkorn, Alfred Morgenstern
The aim of this evaluation is to identify first indicators regarding the efficacy of 225Ac-PSMA-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with 3 cycles of 100 kBq/kgBW 225Ac-PSMA-617 in 2 months intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 weeks. Prostate-specific membrane antigen (PSMA)-PET/CT or PSMA-SPECT/CT were used for baseline staging and imaging follow-up at month six...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29319382/ctc-derived-ar-v7-detection-as-a-prognostic-and-predictive-biomarker-in-advanced-prostate-cancer
#7
Diogo A Bastos, Emmanuel S Antonarakis
Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay has been identified as one of the markers that can be used to predict survival, with added value beyond currently available prognostic factors. Recently, androgen receptor splice variant 7 (AR-V7) detection has been associated with worse outcomes for patients with castration-resistant prostate cancer (CRPC) treated with novel androgen receptor-signaling (ARS) inhibitors such as abiraterone and enzalutamide but not taxane chemotherapies...
January 10, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29316842/integrative-transcriptome-analysis-identifies-genes-and-pathways-associated-with-enzalutamide-resistance-of-prostate-cancer
#8
Subo Qian, Jia Xia, Hailong Liu, Yu Zhang, Lin Zhang, Yongjiang Yu
BACKGROUND: Enzalutamide, a novel androgen receptor (AR) signaling inhibitor, has been widely used to increase survival in patients with castration-resistant prostate cancer. However, resistance to enzalutamide invariably develops. METHODS: To understand the underlying mechanisms of resistance to enzalutamide, we performed integrative analysis on multiple transcriptome datasets to identify those genes constantly up- or down-regulated in response to enzalutamide treatment...
January 9, 2018: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/29302046/p53-status-in-the-primary-tumor-predicts-efficacy-of-subsequent-abiraterone-and-enzalutamide-in-castration-resistant-prostate-cancer
#9
Benjamin L Maughan, Liana B Guedes, Kenneth Boucher, Gaurav Rajoria, Zach Liu, Szczepan Klimek, Roberto Zoino, Emmanuel S Antonarakis, Tamara L Lotan
BACKGROUND: We tested whether tissue-based analysis of p53 and PTEN genomic status in primary tumors is predictive for subsequent sensitivity to abiraterone and enzalutamide in castration-resistant prostate cancer (CRPC). METHODS: We performed a retrospective analysis of 309 consecutive patients with CRPC treated with abiraterone or enzalutamide. Of these, 101 men (33%) had available primary tumor tissue for analysis. We screened for deleterious TP53 missense mutations and PTEN deletions using genetically validated immunohistochemical assays for nuclear accumulation of p53 protein and PTEN protein loss, with sequencing confirmation of TP53 mutations in a subset...
January 4, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29298991/current-approaches-to-incorporation-of-radium-223-in-clinical-practice
#10
REVIEW
Chris Parker, Axel Heidenreich, Sten Nilsson, Neal Shore
BACKGROUND: Treatment options for metastatic castration-resistant prostate cancer (mCRPC) have expanded in recent years and include cytotoxic agents (e.g., docetaxel and cabazitaxel), immunotherapy (e.g., sipuleucel-T), oral hormonal therapies targeting the androgen receptor axis (e.g., enzalutamide and abiraterone), and targeted alpha therapy (e.g., radium-223 dichloride (radium-223)). Although treatment guidelines have been updated to reflect the availability of new agents, it is not easy to apply them in daily clinical practice because recommendations vary depending on patient comorbidities and disease characteristics...
January 3, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29289429/synaptophysin-expression-on-circulating-tumor-cells-in-patients-with-castration-resistant-prostate-cancer-undergoing-treatment-with-abiraterone-acetate-or-enzalutamide
#11
Sumanta K Pal, Miaoling He, Lin Chen, Lixin Yang, Raju Pillai, Przemyslaw Twardowski, JoAnn Hsu, Marcin Kortylewski, Jeremy O Jones
BACKGROUND: With the advent of secondary androgen receptor (AR)-targeted therapies in metastatic castration resistant prostate cancer (PC), nonadenocarcinoma PCs are becoming more prevalent. Many of these cancers express neuroendocrine markers, which may provide biomarkers for emergence of this disease state. We aimed to quantify the expression of synaptophysin (Syp) on circulating tumor cells (CTCs) from serial samples of patients being treated with abiraterone acetate or enzalutamide...
December 27, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29286005/current-concepts-and-trends-in-the-treatment-of-bone-metastases-in-patients-with-advanced-prostate-cancer
#12
REVIEW
Miriam Hegemann, Moritz Maas, Steffen Rausch, Simon Walz, Jens Bedke, Arnulf Stenzl, Tilman Todenhöfer
Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer. In the last decade, the development and approval of substances inhibiting the vicious cycle of bone metastases have enabled the reduction of complications caused by bone metastases in patients with castration-resistant prostate cancer. These drugs have raised awareness of the importance of skeletal-related events which in the meantime represent an important end point also in trials using agents not specifically designed for bone lesions...
December 29, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29285775/systemic-immune-inflammation-index-predicts-the-combined-clinical-outcome-after-sequential-therapy-with-abiraterone-and-docetaxel-for-metastatic-castration-resistant-prostate-cancer-patients
#13
Liancheng Fan, Rui Wang, Chenfei Chi, Wen Cai, Yong Zhang, Hongyang Qian, Xiaoguang Shao, Yanqing Wang, Fan Xu, Jiahua Pan, Yinjie Zhu, Xun Shangguan, Lixin Zhou, Baijun Dong, Wei Xue
OBJECTIVE: To compare the antitumor effect of abiraterone (AA) followed by docetaxel-prednisone (DP) or vice versa in metastatic castration-resistant prostate cancer (mCRPC) patients, and explored factors that might predict combined PSA-PFS, combined rPFS and OS. PATIENTS AND METHODS: We retrospectively analyzed mCRPC patients treated with sequential therapy using DP followed by AA or vice versa. Patients who had received enzalutamide or cabazitaxel were excluded...
December 29, 2017: Prostate
https://www.readbyqxmd.com/read/29277895/enzalutamide-and-cxcr7-inhibitor-combination-treatment-suppresses-cell-growth-and-angiogenic-signaling-in-castration-resistant-prostate-cancer-models
#14
Yong Luo, Abul Kalam Azad, Styliani Karanika, Spyridon P Basourakos, Xuemei Zuo, Jianxiang Wang, Luan Yang, Guang Yang, Dimitrios Korentzelos, Jianhua Yin, Sanghee Park, Penglie Zhang, James J Campbell, Thomas J Schall, Guangwen Cao, Likun Li, Timothy C Thompson
Previous studies have shown that increased levels of chemokine receptor CXCR7 are associated with the increased invasiveness of prostate cancer cells. We now show that CXCR7 expression is upregulated in VCaP and C4-2B cells after enzalutamide (ENZ) treatment. ENZ treatment induced apoptosis (sub-G1) in VCaP and C4-2B cells, and this effect was further increased after combination treatment with ENZ and CCX771, a specific CXCR7 inhibitor. The levels of p-EGFR (Y1068), p-AKT (T308) and VEGFR2 were reduced after ENZ and CCX771 combination treatment compared to single agent treatment...
December 26, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29275450/no-significant-impact-of-response-to-prior-androgen-receptor-axis-targeted-agents-on-the-efficacy-of-subsequent-docetaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer
#15
Hideaki Miyake, Yuto Matsushita, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Takayuki Sugiyama, Atsushi Otsuka
BACKGROUND: To investigate whether the response to an androgen receptor-axis-targeted (ARAT) agent is associated with the efficacy of subsequent docetaxel in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This study included 114 consecutive mCRPC patients, comprising 54 and 60 patients who progressed with abiraterone acetate (AA) and enzalutamide (Enz), respectively, before the introduction of docetaxel. The impact of the response to either ARAT agent on the activity of docetaxel was assessed...
December 23, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29274813/comparison-of-alternative-androgen-receptor-axis-targeted-agent-arata-and-docetaxel-as-second-line-therapy-for-patients-with-metastatic-castration-resistant-prostate-cancer-with-progression-after-initial-arata-in-real-world-clinical-practice-in-japan
#16
Hideaki Miyake, Takayuki Sugiyama, Ryota Aki, Yuto Matsushita, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Atsushi Otsuka
BACKGROUND: The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor-axis-targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA-to-Enz, n = 49; Enz-to-AA, n = 59) and 114 received docetaxel (DTX; AA-to-DTX, n = 54; Enz-to-DTX, n = 60)...
December 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29248236/bipolar-androgen-therapy-in-men-with-metastatic-castration-resistant-prostate-cancer-after-progression-on-enzalutamide-an-open-label-phase-2-multicohort-study
#17
Benjamin A Teply, Hao Wang, Brandon Luber, Rana Sullivan, Irina Rifkind, Ashley Bruns, Avery Spitz, Morgan DeCarli, Victoria Sinibaldi, Caroline F Pratz, Changxue Lu, John L Silberstein, Jun Luo, Michael T Schweizer, Charles G Drake, Michael A Carducci, Channing J Paller, Emmanuel S Antonarakis, Mario A Eisenberger, Samuel R Denmeade
BACKGROUND: Prostate cancer that progresses after enzalutamide treatment is poorly responsive to further antiandrogen therapy, and paradoxically, rapid cycling between high and low serum testosterone concentrations (bipolar androgen therapy [BAT]) in this setting might induce tumour responses. We aimed to evaluate BAT in patients with metastatic castration-resistant prostate cancer that progressed after enzalutamide. METHODS: We did this single-centre, open-label, phase 2, multicohort study in the USA...
December 13, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29247284/third-line-treatment-and-177lu-psma-radioligand-therapy-of-metastatic-castration-resistant-prostate-cancer-a-systematic-review
#18
REVIEW
Finn Edler von Eyben, Giandomenico Roviello, Timo Kiljunen, Christian Uprimny, Irene Virgolini, Kalevi Kairemo, Timo Joensuu
AIMS: There is a controversy as to the relative efficacy of 177Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). METHODS: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines...
December 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29241313/hormonal-treatment-and-quality-of-life-of-prostate-cancer-patients-new-evidences
#19
Marcello Tucci, Gianmarco Leone, Consuelo Buttigliero, Clizia Zichi, Rosario F DI Stefano, Daniele Pignataro, Francesca Vignani, Giorgio V Scagliotti, Massimo DI Maio
Androgen deprivation therapy (ADT) is the mainstay of treatment of patients with relapsed or metastatic hormone-sensitive prostatic carcinoma. The dramatic reduction of serum testosterone levels induced by ADT produces multiple side effects as vasomotor flushing, sexual dysfunction, fatigue, impairment of cognitive function, reduced quality of sleep, gynecomastia and anemia, that are able to decrease health-related quality of life (QoL). In addition, hormonal therapy can interfere with bone metabolism and induce metabolic and cardiovascular complications...
December 14, 2017: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/29234258/toxicity-adverse-events-and-quality-of-life-associated-with-the-treatment-of-metastatic-castration-resistant-prostate-cancer
#20
REVIEW
Senol Tonyali, Hakan Bahadir Haberal, Emrullah Sogutdelen
Objectives: Among males, prostate cancer (PCa) is the most common cancer in Europe and the second most common cancer worldwide, especially in those aged > 70 years. With the advent of novel alternative treatments, survival in patients with advanced PCa has increased. PCa is now considered a chronic disease. Survival is an important endpoint in advanced PCa, as is quality of life (QoL). The effects of the disease and its treatment on patient health-related QoL must be taken into account when selecting the most appropriate treatment options...
November 2017: Current Urology
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