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Enzalutamide resistance

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https://www.readbyqxmd.com/read/28636139/review-of-hplc-and-lc-ms-ms-assays-for-the-determination-of-various-non-steroidal-anti-androgens-nsaa-used-in-the-treatment-of-prostate-cancer
#1
REVIEW
P S Suresh, Nuggehally R Srinivas, Ramesh Mullangi
Prostate cancer is the most common cancer and one of the leading causes for cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first generation non-steroidal anti-androgens (NSAA) namely flutamide, nilutamide, bicalutamide and topilutamide. Most of the prostate cancer patients who are initially responsive develop a most aggressive form of disease called castration-resistant prostate cancer (CRPC). Second generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat CRPC...
June 21, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28628393/early-national-dissemination-of-abiraterone-and-enzalutamide-for-advanced-prostate-cancer-in-medicare-part-d
#2
Megan E V Caram, Tudor Borza, Hye-Sung Min, Jennifer J Griggs, David C Miller, Brent K Hollenbeck, Bhramar Mukherjee, Ted A Skolarus
INTRODUCTION: Abiraterone and enzalutamide were approved by the Food and Drug Administration in 2011 and 2012 to treat men with metastatic castration-resistant prostate cancer (mCRPC). Most men with mCRPC are > 65 years of age and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D data. METHODS: We evaluated the number of prescriptions for abiraterone and enzalutamide by provider specialty and hospital referral region (HRR) using Medicare Part D and Dartmouth Atlas data...
June 19, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28620903/emerging-categories-of-disease-in-advanced-prostate-cancer-and-their-therapeutic-implications
#3
REVIEW
Rahul R Aggarwal, Felix Y Feng, Eric J Small
The treatment of advanced prostate cancer has changed significantly in the last decade, as a result of the introduction of multiple new systemic therapies that have had a positive impact on treatment outcomes. The increasing number of therapies, along with new insights into the biological underpinnings of prostate cancer, have led to a growing appreciation for the heterogeneity of the disease and an awareness of emerging subcategories that have direct therapeutic implications for the practicing clinician. In the metastatic hormone-naive setting, the extent of metastatic disease visible on scans can serve as a useful measure to guide treatment decisions; the addition of docetaxel chemotherapy to hormonal therapy has significant benefit in patients whose scans show more extensive disease...
June 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28614883/-monitoring-of-treatment-for-metastatic-castration-resistant-prostate-cancer
#4
Stefan Hinz
Treatments currently available for metastatic castration-resistant prostate cancer (mCRPC) include abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, and radium-223. However, the optimal sequence of these agents is still unclear, and markers to predict treatment response and facilitate patient selection remain an unmet need. In terms of overall survival, it is crucial that patients receive all treatment options currently available. This requires early detection of progression as an indication for a treatment switch...
May 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28614882/-review-on-quality-of-life-in-crpc-patients
#5
Kurt Miller
Health-related quality of life (HRQoL) deteriorates rapidly in patients with advanced-stage cancer, with patients seriously disturbed by fatigue, sleep disorders, bone pain, constipation and other disease related symptoms. As treatment and prognosis continues to improve, reducing symptoms and improving quality of life with minimum of toxicities have become important therapeutic goals. The effectiveness of abiraterone acetate and enzalutamide in both prolonging life and improving quality of life in asymptomatic or mildly symptomatic patients with metastatic castrations-resistant prostate cancer (mCRPC) has been clinically proven...
May 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28614217/psa-declines-and-survival-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-enzalutamide-a-retrospective-case-report-study
#6
Davide Bosso, Martina Pagliuca, Guru Sonpavde, Gregory Pond, Giuseppe Lucarelli, Sabrina Rossetti, Gaetano Facchini, Sarah Scagliarini, Giacomo Cartenì, Bruno Daniele, Franco Morelli, Matteo Ferro, Livio Puglia, Michela Izzo, Vittorino Montanaro, Teresa Bellelli, Francesca Vitrone, Sabino De Placido, Carlo Buonerba, Giuseppe Di Lorenzo
RATIONALE: PSA responses have been associated with a survival benefit in patients treated with enzalutamide in retrospective analyses. PATIENT CONCERNS: However the prognostic value of PSA declines in highly pretreated patients receiving enzalutamide remains to be defined. DIAGNOSES AND INTERVENTATIONS: Medical records of patients with documented mCRPC treated with enzalutamide between September 2011 and August 2016 were reviewed at multiple participating centers and assessed for overall survival (OS), PSA variations, and other variables of interest...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28609657/ack1-tnk2-regulates-histone-h4-tyr88-phosphorylation-and-ar-gene-expression-in-castration-resistant-prostate-cancer
#7
Kiran Mahajan, Pavani Malla, Harshani R Lawrence, Zhihua Chen, Chandan Kumar-Sinha, Rohit Malik, Sudhanshu Shukla, Jongphil Kim, Domenico Coppola, Nicholas J Lawrence, Nupam P Mahajan
The androgen receptor (AR) is critical for the progression of prostate cancer to a castration-resistant (CRPC) state. AR antagonists are ineffective due to their inability to repress the expression of AR or its splice variant, AR-V7. Here, we report that the tyrosine kinase ACK1 (TNK2) phosphorylates histone H4 at tyrosine 88 upstream of the AR transcription start site. The WDR5/MLL2 complex reads the H4-Y88-phosphorylation marks and deposits the transcriptionally activating H3K4-trimethyl marks promoting AR transcription...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28606735/neutrophil-to-lymphocyte-ratio-in-castration-resistant-prostate-cancer-patients-treated-with-daily-oral-corticosteroids
#8
Niven Mehra, Adam Sharp, David Lorente, David Dolling, Semini Sumanasuriya, Bernadette Johnson, David Dearnaley, Chris Parker, Johann de Bono
BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been shown to be highly prognostic across many tumor types, and predictive of treatment outcome in advanced prostate cancer, and has been postulated to be an indirect measure of tumor inflammation. We evaluated the effect of low-dose steroids on NLR in men suffering from castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: The NLR was evaluated in a prospective randomized phase II trial that compared prednisolone 5 mg twice daily and dexamethasone 0...
May 10, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28604629/androgen-receptor-dependent-and-independent-mechanisms-involved-in-prostate-cancer-therapy-resistance
#9
REVIEW
Daniel J Crona, Young E Whang
Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease...
June 12, 2017: Cancers
https://www.readbyqxmd.com/read/28604117/efficacy-and-safety-of-post-docetaxel-therapies-in-metastatic-castrate-resistant-prostate-cancer-a-systematic-review-of-the-literature
#10
Nicholas Summers, Jacqueline Vanderpuye-Orgle, Marcia Reinhart, Meghan Gallagher, Oliver Sartor
OBJECTIVE: Prostate cancer is a highly prevalent form of cancer in older men and is one of the leading causes of death from cancer in men across the globe. Many therapeutic agents have been approved for patients with metastatic castrate-resistant prostate cancer (mCRPC), particularly as a post-docetaxel treatment strategy. The objective of this systematic literature review was to assess published efficacy and safety data for select mCRPC therapies - such as abiraterone, cabazitaxel, and enzalutamide - in the post-docetaxel setting...
June 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28590268/ar-v7-liquid-biopsy-for-treatment-stratification-in-prostate-cancer-how-close-are-we
#11
Claire Fletcher
PURPOSE OF REVIEW: Recent clinical introduction of the novel antiandrogen, Enzalutamide (Enza), CYP17 inhibitor, Abiraterone (Abi), and the second-generation chemotherapeutic, Cabazitaxel, has increased survival of patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). However, de novo and acquired resistance rates are high. A liquid biopsy that can rapidly, sensitively and robustly identify which patients will respond to treatment in a minimally invasive manner is urgently required to permit switch to a potentially more efficacious drug regimen, thus increasing survival whilst avoiding debilitating side effects associated with unnecessary treatment...
June 5, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28589901/resveratrol-enhances-polyubiquitination-mediated-arv7-degradation-in-prostate-cancer-cells
#12
Sarah Wilson, Lucia Cavero, Dali Tong, Qiuli Liu, Kyla Geary, Nicholas Talamonti, Jing Xu, Junjiang Fu, Jun Jiang, Dianzheng Zhang
Although androgen deprivation therapy (ADT) serves as the primary treatment option for localized or metastatic prostate cancer, most cases eventually develop into castration-resistant prostate cancer (CRPC). However, androgen receptor (AR) continues to be functional in CRPC through various mechanisms, including the development of AR splicing variants, especially ARV7. Since it lacks the ligand binding domain but retains the intact DNA binding domain, ARV7 is constitutively active, which makes ARV7-positive prostate cancer responsive to neither abiraterone nor enzalutamide...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28585559/prostate-cancer-escaping-enzalutamide-malat1-contributes-to-resistance
#13
Louise Stone
No abstract text is available yet for this article.
June 6, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28577511/therapies-for-castration-resistant-prostate-cancer-in-a-new-era-the-indication-of-vintage-hormonal-therapy-chemotherapy-and-the-new-medicines
#14
REVIEW
Atsushi Mizokami, Yoshifumi Kadono, Yasuhide Kitagawa, Kouji Izumi, Hiroyuki Konaka
When advanced prostate cancer recurred during hormonal therapy and became the castration-resistant prostate cancer, "vintage hormonal therapy," such as antiandrogen alternating therapy or estrogen-related hormonal therapy, was widely carried out in Japan until 2013. This vintage hormonal therapy controlled the progression of castration-resistant prostate cancer. When castration-resistant prostate cancer relapses during these therapies, chemotherapy using docetaxel has been carried out subsequently. Since new hormonal therapies using abiraterone acetate and enzalutamide, which improve the prognosis of castration-resistant prostate cancer, became available in Japan from 2014, therapeutic options for castration-resistant prostate cancer have increased...
June 3, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28561699/personalizing-therapy-for-metastatic-prostate-cancer-the-role-of-solid-and-liquid-tumor-biopsies
#15
Terence W Friedlander, Colin C Pritchard, Himisha Beltran
Although biopsies of metastatic prostate cancer are rarely undertaken in the clinical setting, there is increasing interest in developing personalized approaches to therapy by taking into account the genetic and phenotypic changes in an individual tumor. Indeed, analysis of metastatic prostate tumors can predict sensitivity to agents that inhibit DNA repair and resistance to novel hormonal agents, such as abiraterone and enzalutamide, and identify phenotypic changes, such as neuroendocrine differentiation, that have important clinical implications...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28557065/lactate-dehydrogenase-predicts-combined-progression-free-survival-after-sequential-therapy-with-abiraterone-and-enzalutamide-for-patients-with-castration-resistant-prostate-cancer
#16
Keiichiro Mori, Takahiro Kimura, Hajime Onuma, Shoji Kimura, Toshihiro Yamamoto, Hiroshi Sasaki, Jun Miki, Kenta Miki, Shin Egawa
BACKGROUND: An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. METHODS: This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa...
May 30, 2017: Prostate
https://www.readbyqxmd.com/read/28548924/comparing-the-clinical-efficacy-of-abiraterone-acetate-enzalutamide-and-orteronel-in-patients-with-metastatic-castration-resistant-prostate-cancer-by-performing-a-network-meta-analysis-of-eight-randomized-controlled-trials
#17
Minyong Kang, Chang Wook Jeong, Cheol Kwak, Ja Hyeon Ku, Hyeon Hoe Kim
Various novel androgen receptor (AR) targeting drugs have been developed recently and have shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer (mCRPC). However, no consensus has been reached regarding which of these agents provides the most favorable oncological outcomes. Here, we aimed to compare the efficacy of novel AR-targeted agents by performing a network meta-analysis of randomized controlled trials (RCTs). We included eight RCTs for men with mCRPC treated with one of the AR targeting agents: abiraterone acetate, enzalutamide, or orteronel...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28545929/a-simple-hplc-uv-method-for-quantification-of-enzalutamide-and-its-active-metabolite-n-desmethyl-enzalutamide-in-patients-with-metastatic-castration-resistant-prostate-cancer
#18
Alicja Puszkiel, Alain Plé, Olivier Huillard, Gaëlle Noé, Constance Thibault, Stéphane Oudard, François Goldwasser, Michel Vidal, Jérome Alexandre, Benoit Blanchet
Enzalutamide is currently approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). To date, a single liquid chromatographic-tandem mass spectroscopy method is available to measure plasma enzalutamide concentrations in mCRPC patients. In this work, an accurate and sensitive HPLC-UV method has been developed for the simultaneous determination of enzalutamide and its active metabolite, N-desmethyl enzalutamide in plasma from mCRPC patients. Before precipitation of proteins with acetonitrile, samples were spiked with nilutamide (internal standard)...
April 5, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28544352/editorial-comment-to-exploring-the-optimal-sequence-of-abiraterone-and-enzalutamide-in-patients-with-chemotherapy-na%C3%A3-ve-castration-resistant-prostate-cancer-the-kyoto-baltimore-collaboration
#19
Koji Mitsuzuka
No abstract text is available yet for this article.
June 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28536297/androgen-receptor-inhibitor-induced-brcaness-and-parp-inhibition-are-synthetically-lethal-for-castration-resistant-prostate-cancer
#20
Likun Li, Styliani Karanika, Guang Yang, Jiangxiang Wang, Sanghee Park, Bradley M Broom, Ganiraju C Manyam, Wenhui Wu, Yong Luo, Spyridon Basourakos, Jian H Song, Gary E Gallick, Theodoros Karantanos, Dimitrios Korentzelos, Abul Kalam Azad, Jeri Kim, Paul G Corn, Ana M Aparicio, Christopher J Logothetis, Patricia Troncoso, Timothy Heffernan, Carlo Toniatti, Hyun-Sung Lee, Ju-Seog Lee, Xuemei Zuo, Wenjun Chang, Jianhua Yin, Timothy C Thompson
Cancers with loss-of-function mutations in BRCA1 or BRCA2 are deficient in the DNA damage repair pathway called homologous recombination (HR), rendering these cancers exquisitely vulnerable to poly(ADP-ribose) polymerase (PARP) inhibitors. This functional state and therapeutic sensitivity is referred to as "BRCAness" and is most commonly associated with some breast cancer types. Pharmaceutical induction of BRCAness could expand the use of PARP inhibitors to other tumor types. For example, BRCA mutations are present in only ~20% of prostate cancer patients...
May 23, 2017: Science Signaling
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