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Metastatic prostatic cancer clinical treatment

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https://www.readbyqxmd.com/read/28346424/skp2-deficiency-restricts-the-progression-and-stem-cell-features-of-castration-resistant-prostate-cancer-by-destabilizing-twist
#1
D Ruan, J He, C-F Li, H-J Lee, J Liu, H-K Lin, C-H Chan
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28342996/induction-of-neuroendocrine-differentiation-in-prostate-cancer-cells-by-dovitinib-tki-258-and-its-therapeutic-implications
#2
Shalini S Yadav, Jinyi Li, Jennifer A Stockert, Bryan Herzog, James O'Connor, Luis Garzon-Manco, Ramon Parsons, Ashutosh K Tewari, Kamlesh K Yadav
Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC...
March 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28330676/stromal-gene-expression-is-predictive-for-metastatic-primary-prostate-cancer
#3
Fan Mo, Dong Lin, Mandeep Takhar, Varune Rohan Ramnarine, Xin Dong, Robert H Bell, Stanislav V Volik, Kendric Wang, Hui Xue, Yuwei Wang, Anne Haegert, Shawn Anderson, Sonal Brahmbhatt, Nicholas Erho, Xinya Wang, Peter W Gout, James Morris, R Jeffrey Karnes, Robert B Den, Eric A Klein, Edward M Schaeffer, Ashley Ross, Shancheng Ren, S Cenk Sahinalp, Yingrui Li, Xun Xu, Jun Wang, Jian Wang, Martin E Gleave, Elai Davicioni, Yinghao Sun, Yuzhuo Wang, Colin C Collins
BACKGROUND: Clinical grading systems using clinical features alongside nomograms lack precision in guiding treatment decisions in prostate cancer (PCa). There is a critical need for identification of biomarkers that can more accurately stratify patients with primary PCa. OBJECTIVE: To identify a robust prognostic signature to better distinguish indolent from aggressive prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: To develop the signature, whole-genome and whole-transcriptome sequencing was conducted on five PCa patient-derived xenograft (PDX) models collected from independent foci of a single primary tumor and exhibiting variable metastatic phenotypes...
March 19, 2017: European Urology
https://www.readbyqxmd.com/read/28325265/determinants-of-bone-specific-metastasis-in-prostate-cancer
#4
REVIEW
Paolo Manca, Francesco Pantano, Michele Iuliani, Giulia Ribelli, Delia De Lisi, Romano Danesi, Marzia Del Re, Bruno Vincenzi, Giuseppe Tonini, Daniele Santini
Prostate cancer is one of the most common type of cancer in Western countries. Although the majority of patients with PCa have a minimally aggressive disease, some of them will experience relapse and formation of metastasis. Bone metastasis are a major cause of quality of life impairment and death among patients with metastatic prostate cancer. Different "bone targeted therapies" and several follow-up strategies were developed in order to optimize bone metastasis prevention and treatment. Nevertheless there is still a great clinical need of identifying patients more likely to benefit from those interventions as not all patients will develop metastatic disease and not all patients with metastatic disease will develop bone metastasis...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#5
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#6
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28318331/docetaxel-chemotherapy-in-metastatic-castration-resistant-prostate-cancer-cost-of-care-in-medicare-and-commercial-populations
#7
A Armstrong, C Bui, K Fitch, T Goss Sawhney, B Brown, S Flanders, M Balk, J Deangelis, J Chambers
OBJECTIVE: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We used Medicare 5% sample and MarketScan® Commercial (2010 - 2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date...
March 20, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28315704/interleukin-6-and-prostate-cancer-current-developments-and-unsolved-questions
#8
Zoran Culig, Martin Puhr
Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models...
March 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28314971/-when-is-surgical-treatment-indicated-in-metastatic-prostate-cancer-and-what-is-the-scientific-rationale
#9
A Kretschmer, A Herlemann, C G Stief, C Gratzke
BACKGROUND: Recent improvements in imaging diagnostics has led to a rising incidence of oligometastatic prostate cancer and, most notably, an increasing incidence of nodal-only biochemical recurrences. In this clinical setting, systemic therapy is still the treatment of choice. However, there is increasing evidence for surgical approaches in this challenging clinical setting. AIM OF THE STUDY: In this comprehensive review article, current evidence regarding surgical approaches of primary nodal metastases, nodal-only biochemical recurrence following radical prostatectomy, and osseous metastatic prostate cancer will be discussed...
March 17, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28314838/a-phase-i-study-of-abiraterone-acetate-combined-with-bez235-a-dual-pi3k-mtor-inhibitor-in-metastatic-castration-resistant-prostate-cancer
#10
Xiao X Wei, Andrew C Hsieh, Won Kim, Terence Friedlander, Amy M Lin, Mirela Louttit, Charles J Ryan
LESSONS LEARNED: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored. BACKGROUND: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28314611/clinical-outcomes-from-androgen-signaling-directed-therapy-after-treatment-with-abiraterone-acetate-and-prednisone-in-patients-with-metastatic-castration-resistant-prostate-cancer-post-hoc-analysis-of-cou-aa-302
#11
Matthew R Smith, Fred Saad, Dana E Rathkopf, Peter F A Mulders, Johann S de Bono, Eric J Small, Neal D Shore, Karim Fizazi, Thian Kheoh, Jinhui Li, Peter De Porre, Mary B Todd, Margaret K Yu, Charles J Ryan
In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302...
March 14, 2017: European Urology
https://www.readbyqxmd.com/read/28314320/the-clinical-efficacy-of-enzalutamide-in-metastatic-prostate-cancer-prospective-single-center-study
#12
Giuseppe Cicero, Rossella DE Luca, Patrizia Dorangricchia, Francesco Dieli
BACKGROUND/AIM: To evaluate the effectiveness of enzalutamide in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer, progressing after chemotherapy with docetaxel plus prednisone. PATIENTS AND METHODS: A total of 60 patients were enrolled. Reduction in serum prostate-specific antigen (PSA) was assessed as the primary endpoint, while reduction in pain, safety, progression-free survival and overall survival represented secondary endpoints...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303694/lutetium-177-psma-radionuclide-therapy-for-men-with-prostate-cancer-a-review-of-the-current-literature-and-discussion-of-practical-aspects-of-therapy
#13
REVIEW
Louise Emmett, Kathy Willowson, John Violet, Jane Shin, Ashley Blanksby, Jonathan Lee
Prostate-specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high-binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides...
March 2017: Journal of Medical Radiation Sciences
https://www.readbyqxmd.com/read/28291739/a-radiobiological-model-of-metastatic-burden-reduction-for-molecular-radiotherapy-application-to-patients-with-bone-metastases
#14
Ana M Denis-Bacelar, Sarah J Chittenden, Iain Murray, Antigoni Divoli, V Ralph McCready, David P Dearnaley, Joe M O'Sullivan, Bernadette Johnson, Glenn D Flux
Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient...
April 7, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28285412/symptoms-and-impacts-in-non-metastatic-castration-resistant-prostate-cancer-qualitative-study-findings
#15
Erin L Tomaszewski, Pierre Moise, Robert N Krupnick, Jared Downing, Margaret Meyer, Shevani Naidoo, Stefan Holmstrom
OBJECTIVES: We developed a conceptual model to define key concepts associated with patients' experiences with the signs, symptoms, and impacts of non-metastatic castration-resistant prostate cancer (M0-CRPC). METHODS: A targeted review of peer-reviewed literature, and other publicly available information, identified and categorized symptoms and impacts related to early-stage prostate cancer. Semi-structured interviews with five clinical experts helped determine the most relevant and important concepts for patients with M0-CRPC...
March 11, 2017: Patient
https://www.readbyqxmd.com/read/28274892/mir-875-5p-counteracts-epithelial-to-mesenchymal-transition-and-enhances-radiation-response-in-prostate-cancer-through-repression-of-the-egfr-zeb1-axis
#16
Rihan El Bezawy, Denis Cominetti, Nicola Fenderico, Valentina Zuco, Giovanni Luca Beretta, Matteo Dugo, Noemi Arrighetti, Claudio Stucchi, Tiziana Rancati, Riccardo Valdagni, Nadia Zaffaroni, Paolo Gandellini
Radiotherapy is one of the main treatment choices for non-metastatic prostate cancer (PCa), although development of radioresistance limits its effectiveness. Mounting evidence supports the ability of microRNAs to interfere with different radioresistance-associated pathways, suggesting their potential as radiosensitizers. Here, we demonstrate that reconstitution of miR-875-5p, whose expression is down-regulated in PCa clinical samples and directly correlates with that of E-cadherin, was able to enhance radiation response in PCa cell lines and xenografts through EGFR direct targeting...
March 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28274032/disseminated-intravascular-coagulation-and-excessive-fibrinolysis-dic-xfl-syndrome-in-prostate-cancer-a-rare-complicated-disorder
#17
Azhar Bin Amir Hamzah, Yew Maw Choo, Mohamed Azmi Hassali, Fahad Saleem, Ashutosh Kumar Verma
Disseminated Intravascular Coagulation (DIC) develops in patient with prostate cancer, which is manifested by systemic, intracranial, intracavitary or intracutaneous bleeding indicating uncompensated or excessive fibrinolysis (XFL). This case report is a description of a 61-year-old male with metastatic prostate cancer that progressed to manifest DIC. The condition is rare in clinical practice, and even rarer when is coupled with XFL. Treatment was mainly replenishing coagulation factors, platelets and controlling the disease progression with aggressive hormonal therapy...
January 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28272687/prognostic-value-of-twist-1-e-cadherin-and-ezh2-in-prostate-cancer-an-immunohistochemical-study
#18
Aziza E Abdelrahman, Shimaa A Arafa, Ragab A Ahmed
OBJECTIVE: There is an urgent need to identify molecular biomarkers rather than clinical markers to distinguish aggressive prostate cancer from the indolent majority for proper treatment and accurate prediction of prognosis. We aimed to investigate the immunohistochemical expression of epithelial-mesenchymal transition (EMT)-related molecules (Twist-1 and E-cadherin) and the stem cell marker EZH2 in prostate cancer and to assess their ability to identify the high-risk patients, in a trial to explore their prognostic implications...
February 4, 2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28265811/expert-system-for-bone-scan-interpretation-improves-progression-assessment-in-bone-metastatic-prostate-cancer
#19
Fabian Haupt, Georg Berding, Ali Namazian, Florian Wilke, Alena Böker, Axel Merseburger, Lilli Geworski, Markus Antonius Kuczyk, Frank Michael Bengel, Inga Peters
INTRODUCTION: The bone scan index (BSI) was introduced as a quantitative tool for tumor involvement in bone of patients with metastatic prostate cancer (mPCa). The computer-aided diagnosis device for BSI analysis EXINIbone(BSI) seems to represent technical progress for the quantitative assessment of bone involvement. But it is not yet clear if the automated BSI (aBSI) could contribute to improved evaluation of progression in patients under antiandrogens or chemotherapy in contrast to the visual interpretation and/or conventional biomarkers such as the prostate-specific antigen (PSA)...
March 7, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28259476/treatment-outcomes-and-tumor-loss-of-heterozygosity-in-germline-dna-repair-deficient-prostate-cancer
#20
Matti Annala, Werner J Struss, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Daniel Khalaf, Irma-Liisa Seppälä, Alan So, Gregory Lo, Rahul Aggarwal, Eric J Small, Matti Nykter, Martin E Gleave, Kim N Chi, Alexander W Wyatt
BACKGROUND: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to androgen receptor (AR)-directed therapy. OBJECTIVE: To determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies and to establish whether biallelic DNA repair gene loss is detectable in matched circulating tumor DNA (ctDNA)...
March 1, 2017: European Urology
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