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Castrate resistant prostate cancer

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https://www.readbyqxmd.com/read/28812304/management-of-castration-resistant-taxane-resistant-prostate-cancer
#1
Tomasz M Beer
Metastatic castration-resistant prostate cancer that is progressing despite docetaxel chemotherapy is difficult to treat and often aggressive. If not previously used, modern androgen signaling inhibitors have established clinical activity in this setting. Cabazitaxel and radium-223 have also been shown to extend survival in appropriately selected patients. Carboplatin-containing chemotherapy regimens have not been studied in randomized trials with a survival endpoint, but they have demonstrated activity in phase II trials and are occasionally considered in the post-docetaxel setting...
August 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28811771/predictive-value-of-stathmin-1-and-osteopontin-expression-for-taxan-resistance-in-metastatic-castrate-resistant-prostate-cancer
#2
Asude Aksoy, Gokhan Artas, Omur Gokmen Sevindik
OBJECTIVE: Several pathways are known to be activated during metastasis and treatment of cancer. We investigated the role of osteopontin (OPN) and stathmin-1 (STHMN1) in metastatic castrate-resistant (mCRPC). METHODS: We included 30 patients who received at least 6 cycles of taxane regimen for metastatic mPC in the present study. For this study retrospective data was taken from Firat University, Faculty of Medicine, Medical Oncology Department between 2009 and 2015...
May 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28811384/loss-of-spdef-and-gain-of-tgfbi-activity-after-androgen-deprivation-therapy-promote-emt-and-bone-metastasis-of-prostate-cancer
#3
Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Kuo-Ching Jiang, Ai-Ning Shao, Jiaoti Huang, Yen-Nien Liu
Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen-binding protein transforming growth factor-β (TGFβ)-induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR signaling stimulated the activity of the transcription factor SPDEF, which repressed the expression of TGFBI ADT, AR antagonism, or overexpression of TGFBI inhibited the activity of SPDEF and enhanced the proliferation rates of prostate cancer cells...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28811363/targeting-ar-variant-coactivator-interactions-to-exploit-prostate-cancer-vulnerabilities
#4
Fiorella Magani, Stephanie O Peacock, Meghan A Rice, Maria J Martinez, Ann M Greene, Pablo S Magani, Rolando Lyles, Jonathan R Weitz, Kerry L Burnstein
Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced PC. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28811331/targeting-a-single-alternative-polyadenylation-site-coordinately-blocks-expression-of-androgen-receptor-mrna-splice-variants-in-prostate%C3%A2-cancer
#5
Jamie L Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel M Johnson, Olivia Ondigi, Daniel F Voytas, Christine Henzler, Scott M Dehm
Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28809610/phase-iii-study-comparing-a-reduced-dose-of-cabazitaxel-20-mg-m-2-and-the-currently-approved-dose-25-mg-m-2-in-postdocetaxel-patients-with-metastatic-castration-resistant-prostate-cancer-proselica
#6
Mario Eisenberger, Anne-Claire Hardy-Bessard, Choung Soo Kim, Lajos Géczi, Daniel Ford, Loïc Mourey, Joan Carles, Phillip Parente, Albert Font, Gabriel Kacso, Mustapha Chadjaa, Wenping Zhang, John Bernard, Johann de Bono
Purpose Cabazitaxel 25 mg/m(2) (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.gov identifier: NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m(2) (C20) versus C25 in postdocetaxel patients with mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability of disease per Response Evaluation Criteria in Solid Tumors (RECIST), and region, and randomly assigned to receive C20 or C25...
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28809609/the-who-what-and-how-of-cabazitaxel-treatment-in-metastatic-castration-resistant-prostate-cancer
#7
Tian Zhang, Andrew J Armstrong
No abstract text is available yet for this article.
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28808045/fighting-tubulin-targeting-anticancer-drug-toxicity-and-resistance
#8
REVIEW
Roberta Visconti, Domenico Grieco
Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD efficacy, reducing the acquisition of resistance by the tumor and side effects from the drug and/or its vehicle...
September 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28806246/response-assessment-of-223ra-treatment-should-a-fluorocholine-pet-ct-be-performed
#9
Ana María García Vicente, Ángel Soriano Castrejón, Ruth Alvarez Cabellos, Belén Sanchez Gil, Nicolás Mohedano Mohedano
We present 3 cases of patients with castration-resistant prostate cancer and bone metastases treated with Ra, belonging to our prospective and multicenter ChoPET-Rad study. All patients underwent clinical, hematological, and biochemical monitoring between each Ra administration. Initial and follow-up F-fluorocholine PET/CT and Tc-biphosphonate bone scintigraphy were performed previously and after the third Ra administration. Both techniques correctly established the response to treatment, in agreement to the biochemical response, although differences in the disease expression (concordant and discordant patterns) were found because of the different radiotracer biodistribution and molecular information derived from them...
August 12, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28804908/influence-of-abiraterone-acetate-on-neuroendocrine-differentiation-in-chemotherapy-naive-metastatic-castration-resistant-prostate-cancer
#10
Baijun Dong, Liancheng Fan, Yanqing Wang, Chenfei Chi, Xiaowei Ma, Rui Wang, Wen Cai, Xiaoguang Shao, Jiahua Pan, Yinjie Zhu, Xun Shangguan, Zhixiang Xin, Jianian Hu, Shaowei Xie, Xiaonan Kang, Lixin Zhou, Wei Xue
BACKGROUND: To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted an analysis in 115 chemotherapy-naïve mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment...
August 14, 2017: Prostate
https://www.readbyqxmd.com/read/28804543/light-of-dna-alkylating-agents-in-castration-resistant-prostate-cancer-cells-a-novel-mixed-egfr-dna-targeting-combi-molecule
#11
Guan-Can Liang, Hao-Feng Zheng, Yan-Xiong Chen, Teng-Cheng Li, Wei Liu, You-Qiang Fang
OBJECTIVE: The mechanism underlying the therapeutic effects of combi-molecule JDF12 on prostate cancer (PCa) DU145 cells remains still unclear. This study aimed to investigate the proteomic profile after JDF12 treatment in DU145 cells by comparing with that in Iressa treated cells and untreated cells. METHODS: MTT was used to evaluate drug cytotoxicity, DAPI staining was done to assess apoptosis of cells, and flow cytometry was used to analyze cell cycle. iTRAQ and qPCR were employed to obtain the proteomic profiles of JDF12 treated, Iressa treated, and untreated DU145 cells, and validate the expression of selected differentially expressed proteins, respectively...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28801852/phase-1-study-of-darolutamide-odm-201-a-new-generation-androgen-receptor-antagonist-in-japanese-patients-with-metastatic-castration-resistant-prostate-cancer
#12
Nobuaki Matsubara, Hirofumi Mukai, Ako Hosono, Mai Onomura, Masaoki Sasaki, Yoko Yajima, Kensei Hashizume, Masanobu Yasuda, Miho Uemura, Christian Zurth
PURPOSE: This trial assessed the safety, pharmacokinetics, and efficacy of darolutamide (ODM-201), a new-generation nonsteroidal androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: In this open-label, nonrandomized, two-cohort, dose-escalating phase 1 study, Japanese patients with mCRPC were enrolled after a screening period. In the single-dose period (≈1 week), darolutamide was administered at 300 mg (Cohort 1) or 600 mg (Cohort 2) on day-5 (fasting state) and day-2 (fed condition)...
August 11, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28800286/clinical-pet-imaging-in-prostate-cancer
#13
Kathryn L Wallitt, Sairah R Khan, Suraiya Dubash, Henry H Tam, Sameer Khan, Tara D Barwick
Prostate cancer is the second most common cancer in men worldwide, with a wide spectrum of biologic behavior ranging from indolent low-risk disease to highly aggressive castration-resistant prostate cancer. Conventional imaging with computed tomography, magnetic resonance imaging, and bone scintigraphy is limited for the detection of nodal disease and distant bone metastases. In addition, advances in the available therapeutic options, both localized and systemic, drive the requirement for precise diagnostic and prognostic tools to refine the individual therapeutic approach at various times in the management of patients with prostate cancer...
August 11, 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28797685/predicting-response-and-recognizing-resistance-improving-outcomes-in-patients-with-castration-resistant-prostate-cancer
#14
REVIEW
Neal Shore, Axel Heidenreich, Fred Saad
Optimal sequencing strategies for approved agents in metastatic castration-resistant prostate cancer (mCRPC) are unclear. Retrospective clinical studies suggest cross-resistance between specific therapies. This review assesses treatment decisions for mCRPC. Increased use of chemohormonal therapy in castration-sensitive disease may affect subsequent treatment decisions in mCRPC. Initial abiraterone or enzalutamide treatment may result in cross-resistance for subsequent AR-targeted therapy. Clinical responses may be seen in both docetaxel- and cabazitaxel-treated patients progressing after treatment with abiraterone or enzalutamide...
August 7, 2017: Urology
https://www.readbyqxmd.com/read/28797006/amiloride-is-effective-in-the-management-of-abiraterone-induced-mineralocorticoid-excess-syndrome-without-interfering-with-its-antineoplastic-activity
#15
Francesca Bedussi, Diego Galli, Martina Fragni, Francesca Valcamonico, Elisa Rossini, Alberto Dalla Volta, Sara Vezzoli, Elisa Roca, Vittorio Ferrari, Barbara Lazzari, Maurizio Memo, Sandra Sigala, Alfredo Berruti
BACKGROUND: The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES). METHODS: The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC)...
August 11, 2017: Pharmacology
https://www.readbyqxmd.com/read/28796922/long-non-coding-rnas-and-prostate-cancer
#16
REVIEW
Aya Misawa, Ken-Ichi Takayama, Satoshi Inoue
Long non-coding RNAs (lncRNAs) are RNA transcripts larger than 200 nucleotides that do not code for proteins whose aberrant expression has been documented in various types of cancer, including prostate cancer. The lack of appropriate sensitive and specific biomarkers for prostate cancer has led to over-diagnosis and overtreatment, making lncRNAs promising novel biomarkers as well as therapeutic targets for the disease. This review attempts to summarize the current knowledge of lncRNA expression patterns and mechanisms in prostate cancer, which contribute to carcinogenesis...
August 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/28795333/patient-characteristics-and-overall-survival-in-patients-with-post-docetaxel-metastatic-castration-resistant-prostate-cancer-in-the-community-setting
#17
William K Oh, Raymond Miao, Francis Vekeman, Jennifer Sung, Wendy Y Cheng, Marjolaine Gauthier-Loiselle, Ravinder Dhawan, Mei Sheng Duh
It is unclear how treatment sequencing for metastatic castration-resistant prostate cancer (mCRPC) affects real-world patient outcomes. We assessed treatment sequences, patient characteristics and overall survival (OS) in post-docetaxel mCRPC patients. mCRPC patients receiving second-line cabazitaxel or androgen receptor-targeted therapy (ART; abiraterone/enzalutamide) post-docetaxel were identified using electronic medical records. OS was assessed from second-line therapy initiation using Cox regressions adjusting for: metastases; prostate-specific antigen (PSA); hemoglobin; alkaline phosphatase (ALP); albumin; second-line therapy initiation year...
August 10, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28795303/the-feasibility-of-prostate-specific-membrane-antigen-positron-emission-tomography-psma-pet-ct-guided-radiotherapy-in-oligometastatic-prostate-cancer-patients
#18
O C Guler, B Engels, C Onal, H Everaert, R Van den Begin, T Gevaert, M de Ridder
BACKGROUND: To investigate the efficacy and toxicity of 68Ga-PSMA-HBED-CC ((68)Ga-PSMA) PET-CT-guided RT in the treatment of oligometastatic prostate cancer retrospectively. METHODS: A total of 23 prostate cancer patients with biochemical relapse, of which 13 were castration sensitive (CS) and 10 castration resistant (CR), were treated with intensity-modulated and image-guided RT (IMRT-IGRT) on ≤3 metastases detected by (68)Ga PSMA PET-CT. Androgen deprivation therapy was continued in CR patients...
August 9, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28794807/prognostic-and-predictive-biomarkers-in-prostate-cancer-latest-evidence-and-clinical-implications
#19
REVIEW
Naoki Terada, Shusuke Akamatsu, Takashi Kobayashi, Takahiro Inoue, Osamu Ogawa, Emmanuel S Antonarakis
Advances in our understanding of the mechanisms driving castration-resistant prostate cancer have promoted the development of several new drugs including androgen receptor-directed therapy and chemotherapy. Concomitant docetaxel treatment at the beginning of hormonal therapy for metastatic prostate cancer has resulted in longer overall survival than with hormonal therapy alone. Elucidating an appropriate treatment sequence using these therapies is important for maximizing clinical benefit in castration-sensitive and castration-resistant prostate cancer patients...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28790846/the-association-between-spink1-and-clinical-outcomes-in-patients-with-prostate-cancer-a-systematic-review-and-meta-analysis
#20
Xingming Zhang, Xiaoxue Yin, Pengfei Shen, Guangxi Sun, Yaojing Yang, Jiandong Liu, Ni Chen, Hao Zeng
Evidence of the prognostic role of serine peptidase inhibitor Kazal type 1 (SPINK1) in prostate cancer (PCa) is controversial. The aim of this study was, therefore, to evaluate the association between SPINK1 and clinical outcomes in PCa. Searches were made of PubMed, Medline, Embase, and the China Biology Medicine disc (CBMdisc) up to January 2017. The Newcastle-Ottawa Scale was used to assess the risk of bias of included studies. RevMan software was used to perform meta-analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was employed for assessing the quality of the evidence...
2017: OncoTargets and Therapy
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