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Castration resistant

Tatsuaki Daimon, Takeo Kosaka, Mototsugu Oya
Docetaxel chemotherapy for metastatic castration resistant prostate cancer patients has been thought palliative because the radiological response rate is low and durable response is rare. The patient was a 64-year-old man who was diagnosed with cT3aN0M0 prostate cancer and underwent external beam radiation therapy as the initial treatment. He underwent androgen deprivation therapy and 8 cycles of docetaxel chemotherapy. His PSA level decreased and became undetectable and the disease was confirmed to be stable by radiological examination...
2016: American Journal of Clinical and Experimental Urology
Kambiz Rahbar, Hojjat Ahmadzadehfar, Clemens Kratochwil, Uwe Haberkorn, Michael Schäfers, Markus Essler, Richard P Baum, Harshad R Kulkarani, Matthias Schmidt, Peter Bartenstein, Andreas Pfestroff, Ulf Lützen, Marlies Marx, Vikas Prasad, Winfried Brenner, Alexander Heinzel, Juri Ruf, Philipp Tobias Meyer, Martin Heuschkel, Maria Eveslage, Martin Bögemann, Wolfgang Peter Fendler, Bernd Joachim Krause
: (177)Lutetium labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of (177)Lu-PSMA-617 in a large cohort of patients. METHODS: 145 patients (median age 73 years, range 43-88) with mCRPC were treated with (177)Lu-PSMA-617 in 12 therapy centres between February 2014 and July 2015 with one to four therapy cycles and an activity range of 2 to 8 GBq per cycle...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Eiman Mukhtar, Vaqar M Adhami, Imtiaz A Siddiqui, Ajit K Verma, Hasan Mukhtar
Although treatment of prostate cancer (PCa) has improved over the past several years, taxanes such as cabazitaxel remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant PCa. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule stabilizing agent and inhibits PCa cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types...
October 7, 2016: Molecular Cancer Therapeutics
Nada Lallous, Eric Leblanc, Ravi Sn Munuganti, Mohamed D H Hassona, Nader Al Nakouzi, Shannon Awrey, Helene Morin, Mani Roshan-Moniri, Kriti Singh, Sam Lawn, Takeshi Yamazaki, Hans H Adomat, Christophe Andre, Mads Daugaard, Robert N Young, Emma S Tomlinson Guns, Paul S Rennie, Artem Cherkasov
The development of new anti-androgens such as enzalutamide or androgen synthesis inhibitors like abiraterone have improved patient outcomes in the treatment of advanced prostate cancer (PCa). However, due to the development of drug resistance and tumor cell survival, the majority of these patients progress to the refractory state of castration-resistant prostate cancer (CRPC). Thus, newer therapeutic agents and a better understanding of their mode of action are needed for treating these CRPC patients. We demonstrated previously that targeting the Binding Function 3 (BF3) pocket of the androgen receptor (AR) has great potential for treating patients with CRPC...
October 7, 2016: Molecular Cancer Therapeutics
Ion Cristobal, Blanca Torrejón, Manuel Pedregal, Federico G Rojo, Jesús García-Foncillas
Dear Editor, We have read with great interest the recent published manuscript by Caiazza et al. (2016), which provides novel exciting findings about the potential therapeutic value of enzalutamide in patients with androgen receptor (AR)-positive triple negative breast cancer (TNBC). Some previous studies have shown promising antitumor effects of this drug in breast tumors. Thus, enzalutamide-mediated AR inhibition has been reported to reduce proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis of TNBC cells in vitro and decrease viability of TNBC xenografts in vivo (Cochrane et al...
October 20, 2016: Endocrine-related Cancer
Matthew I Milowsky, Matthew D Galsky, Michael J Morris, Daniel J Crona, Daniel J George, Robert Dreicer, Kin Tse, Jesika Petruck, Iain J Webb, Neil H Bander, David M Nanus, Howard I Scher
BACKGROUND: This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer. PATIENTS AND METHODS: A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165mg/m(2); 12 patients); every 2 weeks (120, 168, 236, and 330mg/m(2); 15 patients); every 3 weeks (330 and 426mg/m(2); 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330mg/m(2); 17 patients)...
October 17, 2016: Urologic Oncology
Silvana Giacinti, Paolo Carlini, Michela Roberto, Maria Bassanelli, Lidia Strigari, Francesco Pavese, Anna M Aschelter, Alessandra Felici, Maurizio Valeriani, Francesco Cognetti, Paolo Marchetti
Abiraterone acetate (AA) demonstrated its efficacy in the treatment of patients with metastatic castration resistance prostate cancer (mCRPC) in predocetaxel and postdocetaxel setting. However, we learn from pivotal studies that forms of primary and acquired resistance to this drug exist. Patient selection becomes so crucial to optimize treatment results. Potential predictive biomarkers have been identified but are not yet validated. In this scenario, clinical features and disease characteristics may still be of value in selecting patients for different treatments...
October 19, 2016: Anti-cancer Drugs
Claire Levrier, Martin C Sadowski, Anja Rockstroh, Brian Gabrielli, Maria Kavallaris, Melanie Lehman, Rohan A Davis, Colleen C Nelson
The lack of a cure for metastatic castrate-resistant prostate cancer (mCRPC) highlights the urgent need for more efficient drugs to fight this disease. Here, we report the mechanism of action of the natural product 6α-acetoxyanopterine (6-AA) in prostate cancer cells. At low nanomolar doses, this potent cytotoxic alkaloid from the Australian endemic tree Anopterus macleayanus induced a strong accumulation of LNCaP and PC-3 (prostate cancer) cells as well as HeLa (cervical cancer) cells in mitosis, severe mitotic spindle defects and asymmetric cell divisions, ultimately leading to mitotic catastrophe accompanied by cell death through apoptosis...
October 19, 2016: Molecular Cancer Therapeutics
Shuai Gao, Yanfei Gao, Housheng Hansen He, Dong Han, Wanting Han, Amy Avery, Jill A Macoska, Xiaming Liu, Sen Chen, Fen Ma, Shaoyong Chen, Steven P Balk, Changmeng Cai
Although well characterized as a transcriptional activator that drives prostate cancer (PCa) growth, androgen receptor (AR) can function as a transcriptional repressor, and high-level androgens can suppress PCa proliferation. The molecular basis for this repression activity remains to be determined. Genes required for DNA replication are highly enriched among androgen-repressed genes, and AR is recruited to the majority of these genes, where it rapidly represses their transcription. This activity is enhanced in PCa cells expressing high AR levels and is mediated by recruitment of hypophosphorylated retinoblastoma protein (Rb)...
October 18, 2016: Cell Reports
Michael T Schweizer, Heather H Cheng, Maria S Tretiakova, Funda Vakar-Lopez, Nola Klemfuss, Eric Q Konnick, Elahe A Mostaghel, Peter S Nelson, Evan Y Yu, R Bruce Montgomery, Lawrence D True, Colin C Pritchard
Precision oncology entails making treatment decisions based on a tumor's molecular characteristics. For prostate cancer, identifying clinically relevant molecular subgroups is challenging, as molecular profiling is not routine outside of academic centers. Since histologic variants of other cancers correlates with specific genomic alterations, we sought to determine if ductal adenocarcinoma of the prostate (dPC) - a rare and aggressive histopathologic variant - was associated with any recurrent actionable mutations...
October 15, 2016: Oncotarget
Shabbir M H Alibhai, Salman Aziz, Tharsika Manokumar, Narhari Timilshina, Henriette Breunis
OBJECTIVE: Since the benefits of chemotherapy in treating older men with metastatic castration-resistant prostate cancer (mCRPC) are modest, validated tools that predict the risk of treatment toxicity may aid clinical decision-making. Whether these tools are better than oncologist judgment remains unclear. We compared the Cancer and Aging Research Group (CARG) tool, the Vulnerable Elders Survey-13 (VES-13), and oncologist judgment in predicting toxicity in men with mCRPC undergoing chemotherapy...
October 15, 2016: Journal of Geriatric Oncology
Yoko Yamada, Nobuaki Matsubara, Ken-Ichi Tabata, Takefumi Satoh, Naoto Kamiya, Hiroyoshi Suzuki, Takashi Kawahara, Hiroji Uemura, Akihiro Yano, Satoru Kawakami
BACKGROUND: Both abiraterone acetate (AA) and enzalutamide are promising agents for patients with pre- and post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC). Several retrospective analysis suggested clinical cross-resistance between these agents in patients previously treated with docetaxel. However, data on the antitumor activity of AA as a second androgen receptor-targeting new agent after the failure of enzalutamide in chemotherapy-naive mCRPC patients is unavailable...
October 18, 2016: BMC Research Notes
Chad R Ritch, Michael S Cookson
Docetaxel based chemotherapy showed survival benefit and emerged as the mainstay of treatment for castration resistant prostate cancer (CRPC) in 2004. However, therapeutic options have expanded rapidly since 2011. The spectrum of new agents is broad and includes drugs that target the androgen axis (enzalutamide, abiraterone), immunotherapy (sipuleucel-T), bone seeking radionuclides (radium-223), and second line chemotherapy (cabazitaxel). In addition, new agents have been developed to reduce skeletal related events (denosumab)...
October 17, 2016: BMJ: British Medical Journal
Luis Ramudo Cela, Jesús Balea Filgueiras, José Ramón Vizoso Hermida, Isabel Martín Herranz
Abiraterone acetate is a potent and irreversible inhibitor of cytochrome p450 17A1 that suppresses androgen synthesis. It is approved for chemotherapy-naive and docetaxel-treated patients with metastatic castration-resistant prostate cancer. We describe the protocol for use of abiraterone in metastatic castration-resistant prostate cancer chemotherapy naive patients has been implanted in our centre and we review the cases of those patients whose adverse effects have forced the discontinuation of treatment. The side effects fit the safety profile of abiraterone, speed of their appearance and severity indicate that you should perform a thorough follow-up of these patients especially in the early phases of treatment...
October 16, 2016: Journal of Oncology Pharmacy Practice
Axel Bode, Kambiz Rahbar, Julia Konnert, Martin Bögemann, Lars Stegger
A 66-year-old man with castration-resistant prostate carcinoma and multiple symptomatic bone mestastases was considered for Ra-dichloride (Xofigo) therapy. Staging with Ga-PSMA-PET/CT revealed additional extensive tumor involvement of the spine without relevant uptake in bone scintigraphy. Based on this imaging result, the patient was rescheduled for a PSMA-targeted therapy. Additional Ga-PSMA-PET/CT may have a considerable benefit for patients considered for Xofigo.
October 5, 2016: Clinical Nuclear Medicine
Daniel H Hovelson, Scott A Tomlins
Molecular biomarkers play little role in the current treatment of metastatic castration-resistant prostate cancer (CRPC). The advent of next-generation sequencing (NGS) has enabled the comprehensive molecular characterization of the genomic and transcriptomic landscape of both untreated primary prostate cancer and CRPC. Recent studies demonstrating the feasibility of interinstitution studies obtaining and NGS profiling of metastatic biopsies, targeted NGS approaches applicable to routine formalin-fixed, paraffin-embedded specimens, and NGS approaches applicable to circulating DNA and circulating tumor cells portend near-term adoption of NGS approaches in the management and treatment of CRPC...
September 2016: Cancer Journal
Elena Castro, Joaquin Mateo, David Olmos, Johann S de Bono
Several genomic studies have identified DNA repair gene defects in prostate cancer in the last 5 years. The mechanisms by which these DNA repair defects promote carcinogenesis and tumor progression in the prostate have not been fully elucidated, but their presence in at least 20-25% of metastatic castration-resistant prostate cancers (CRPCs) provides an opportunity for a therapeutic strategy that turns a tumor strength into its weakness and may lead to arguably the first molecularly stratified treatment for this disease...
September 2016: Cancer Journal
Min Yuen Teo, Michael J Morris
Prostate-specific membrane antigen (PSMA) is highly expressed on both benign and malignant prostatic tissue. Prostate-specific membrane antigen-directed therapy is conceptually promising, with a potential to additionally serve as a theranostic model in management of advanced prostate cancer. To date, various approaches have been devised and tested, including radiolabeled PSMA antibodies and inhibitor and antibody-drug conjugates. However, development and progress have faced challenges in determining the optimal combination of payload, PSMA-binding moiety, and linker technology...
September 2016: Cancer Journal
Oliver Sartor
Radiopharmaceuticals used in the treatment of castrate-resistant prostate cancer are reviewed herein with an emphasis on sequential and combination therapies. Four bone-seeking radiopharmaceuticals had been approved in the United States. Three of these are β-emitters (phosphorus-32, strontium-89, samarium-153-ethylenediaminetetramethylene-phosphonic acid) that are approved for palliative purposes. One α-emitter (radium-223 [Ra]) is approved for prolongation of survival in bone metastatic castrate-resistant prostate cancer...
September 2016: Cancer Journal
Oladapo Yeku, Susan F Slovin
Immunotherapy for castration-resistant prostate cancer has continued to be an area of active research over the last several years. The enthusiasm of this approach has been based on the assumption of better tolerability and that using the body's own immune system may be more effective than either hormonal or chemotherapy. Sipuleucel-T, a dendritic cell-based vaccine, is the only approved agent in this class for the management of castrate-resistant prostate cancer. Although sipuleucel-T increases overall survival without any significant changes in progression-free survival, other forms of immunotherapy such as PSA-TRICOM, ipilimumab, and chimeric antigen receptor T cell therapy are in advanced stages of clinical development...
September 2016: Cancer Journal
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