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https://www.readbyqxmd.com/read/29569310/molecular-model-for-neuroendocrine-prostate-cancer-progression
#1
REVIEW
Ruiqi Chen, Xuesen Dong, Martin Gleave
Prostate cancer (PCa) is the most common form of cancer for men in the developed world and the second leading cause of cancer-related deaths. While advanced PCa is initially controlled with hormonal therapies targeting the androgen receptor (AR) pathway, recurrence occurs due to the emergence of lethal castration-resistant PCa (CRPC). Despite newer AR pathway inhibitors that prolong survival, resistance still emerges, most often with rising PSA indicative of AR-driven activity, but increasingly as non-AR-driven cancer...
March 22, 2018: BJU International
https://www.readbyqxmd.com/read/29555975/orphan-nuclear-receptor-tlx-contributes-to-androgen-insensitivity-in-castration-resistant-prostate-cancer-via-its-repression-of-androgen-receptor-transcription
#2
Lin Jia, Dinglan Wu, Yuliang Wang, Wenxing You, Zhu Wang, Lijia Xiao, Ganhui Cai, Zhenyu Xu, Chang Zou, Fei Wang, Jeremy Yuen-Chun Teoh, Chi-Fai Ng, Shan Yu, Franky L Chan
The metastatic castration-resistant prostate cancer (CRPC) is a lethal form of prostate cancer, in which the expression of androgen receptor (AR) is highly heterogeneous. Indeed, lower AR expression and attenuated AR signature activity is shown in CRPC tissues, especially in the subset of neuroendocrine prostate cancer (NEPC) and prostate cancer stem-like cells (PCSCs). However, the significance of AR downregulation in androgen insensitivity and de-differentiation of tumor cells in CRPC is poorly understood and much neglected...
March 20, 2018: Oncogene
https://www.readbyqxmd.com/read/29549167/tetrandrine-tet-induces-death-receptors-apo-trail-r1-dr4-and-apo-trail-r2-dr5-and-sensitizes-prostate-cancer-cells-to-trail-induced-apoptosis
#3
Gauri Shishodia, Sweaty Koul, Qin Dong, Hari K Koul
TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells, but not in normal cells, as such is a promising therapeutic agent. However, therapeutic resistance limits its clinical use in many malignancies including prostate cancer (PCa). Strategies to sensitize cancer cells to TRAIL are urgently needed. We demonstrate here that small-molecule Tetrandrine (TET) potentially sensitizes previously resistant (LNCaP and C4-2B cells) and mildly sensitive (PC3 cells) PCa cells to TRAIL- induced apoptosis, and they do so by up-regulating mRNA expression and protein levels of death receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5)...
March 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29487201/heterochromatin-protein-1%C3%AE-mediates-development-and-aggressiveness-of-neuroendocrine-prostate-cancer
#4
Xinpei Ci, Jun Hao, Xin Dong, Stephen Y C Choi, Hui Xue, Rebecca Wu, Sifeng Qu, Peter W Gout, Fang Zhang, Anne M Haegert, Ladan Fazil, Francesco Crea, Christopher J Ong, Amina Zoubedi, Housheng H He, Martin E Gleave, Colin C Collins, Dong Lin, Yuzhuo Wang
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer (PCa) arising mostly from adenocarcinoma via NE transdifferentiation following androgen deprivation therapy. Mechanisms contributing to both NEPC development and its aggressiveness remain elusive. In light of the fact that hyperchromatic nuclei are a distinguishing histopathological feature of NEPC, we utilized transcriptomic analyses of our patient-derived xenograft (PDX) models, multiple clinical cohorts, and genetically engineered mouse models to identify 36 heterochromatin-related genes that are significantly enriched in NEPC...
February 27, 2018: Cancer Research
https://www.readbyqxmd.com/read/29460922/cellular-plasticity-and-the-neuroendocrine-phenotype-in-prostate-cancer
#5
REVIEW
Alastair H Davies, Himisha Beltran, Amina Zoubeidi
The success of next-generation androgen receptor (AR) pathway inhibitors, such as abiraterone acetate and enzalutamide, in treating prostate cancer has been hampered by the emergence of drug resistance. This acquired drug resistance is driven, in part, by the ability of prostate cancer cells to change their phenotype to adopt AR-independent pathways for growth and survival. Around one-quarter of resistant prostate tumours comprise cells that have undergone cellular reprogramming to become AR-independent and to acquire a continuum of neuroendocrine characteristics...
February 20, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29230006/platinum-sensitivity-in-metastatic-prostate-cancer-does-histology-matter
#6
Michael S Humeniuk, Rajan T Gupta, Patrick Healy, Megan McNamara, Sundhar Ramalingam, Michael Harrison, Daniel George, Tian Zhang, Yuan Wu, Andrew J Armstrong
BACKGROUND: Platinum-based chemotherapy is effective in men with neuroendocrine prostate cancer (NEPC), but it is unclear whether histology (adenocarcinoma vs. non-adenocarcinoma NEPC variants) is predictive of platinum sensitivity. Given that NEPC exists as a spectrum, there may be men with adenocarcinoma who might benefit from platinum chemotherapy, particularly those men with DNA repair defects. METHODS: This was a retrospective study of all of the men seen at Duke University since 2005 who had metastatic castration-resistant prostate cancer (mCRPC) and were treated with a platinum agent...
December 11, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29228680/long-noncoding-rna-miat-promotes-non-small-cell-lung-cancer-proliferation-and-metastasis-through-mmp9-activation
#7
I-Lu Lai, Chin-An Yang, Pei-Chin Lin, Wen-Ling Chan, Ya-Ting Lee, Ju-Chen Yen, Ya-Sian Chang, Jan-Gowth Chang
Long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis. Myocardial infarction-associated transcript (MIAT), originally isolated as a candidate gene for myocardial infarction, has been found to act as an oncogene in chronic lymphocytic leukaemias and neuroendocrine prostate cancer (NEPC); however, little is known about its expression pattern, biological function, and underlying mechanism in non-small cell lung cancer (NSCLC). In this study, we observed that MIAT expression was upregulated in NSCLC, and its overexpression was associated with advanced tumor stage...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156689/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#8
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138344/targeting-the-mycn-parp-dna-damage-response-pathway-in-neuroendocrine-prostate-cancer
#9
Wei Zhang, Bo Liu, Wenhui Wu, Likun Li, Bradley M Broom, Spyridon P Basourakos, Dimitrios Korentzelos, Yang Luan, Jianxiang Wang, Guang Yang, Sanghee Park, Abul Kalam Azad, Xuhong Cao, Jeri Kim, Paul G Corn, Christopher J Logothetis, Ana M Aparicio, Arul M Chinnaiyan, Nora Navone, Patricia Troncoso, Timothy C Thompson
Purpose: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC). Experimental Design and Results: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public data sets and a panel of 28 PDX models, we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro...
February 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29132337/gene-expression-signatures-of-neuroendocrine-prostate-cancer-and-primary-small-cell-prostatic-carcinoma
#10
Harrison K Tsai, Jonathan Lehrer, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, Tamara L Lotan
BACKGROUND: Neuroendocrine prostate cancer (NEPC) may be rising in prevalence as patients with advanced prostate cancer potentially develop resistance to contemporary anti-androgen treatment through a neuroendocrine phenotype. While prior studies comparing NEPC and prostatic adenocarcinoma have identified important candidates for targeted therapy, most have relied on few NEPC patients due to disease rarity, resulting in thousands of differentially expressed genes collectively and offering an opportunity for meta-analysis...
November 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29063171/-neuroendocrine-prostate-cancer
#11
S Tritschler, R Erdelkamp, C Stief, M Hentrich
Neuroendocrine prostate cancer (NEPC) mostly occurs as a treatment-emergent adaptive response under the pressure of intensive androgen deprivation treatment (t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary small cell prostate cancer is very rare (<1%). A t‑NEPC should be clinically suspected in patients who have particularly aggressive mCRPC but a disproportionately low prostate-specific antigen (PSA) level and elevated neuroendocrine tumor markers, such as chromogranin A and neuron-specific enolase...
November 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28978002/establishment-of-a-neuroendocrine-prostate-cancer-model-driven-by-the-rna-splicing-factor-srrm4
#12
Yinan Li, Ruiqi Chen, Mary Bowden, Fan Mo, Yen-Yi Lin, Martin Gleave, Colin Collins, Xuesen Dong
Neuroendocrine prostate cancer (NEPC) is becoming more prevalent as more potent androgen receptor (AR) pathway inhibitors are applied to patients with metastatic tumors. However, there are limited cell and xenograft models currently available, hindering the investigation of signal pathways involved in regulating NEPC progression and the design of high throughput screening assays for inhibitors to treat NEPC patients. Here, we report an NEPC model, LnNE, that is derived from prostate adenocarcinoma cells and has global similarity in transcription and RNA splicing to tumors from NEPC patients...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28790115/msh2-loss-in-primary-prostate-cancer
#13
Liana B Guedes, Emmanuel S Antonarakis, Michael T Schweizer, Nooshin Mirkheshti, Fawaz Almutairi, Jong Chul Park, Stephanie Glavaris, Jessica Hicks, Mario A Eisenberger, Angelo M De Marzo, Jonathan I Epstein, William B Isaacs, James R Eshleman, Colin C Pritchard, Tamara L Lotan
Purpose: Inactivation of mismatch repair (MMR) genes may predict sensitivity to immunotherapy in metastatic prostate cancers. We studied primary prostate tumors with MMR defects.Experimental Design: A total of 1,133 primary prostatic adenocarcinomas and 43 prostatic small cell carcinomas (NEPC) were screened by MSH2 immunohistochemistry with confirmation by next-generation sequencing (NGS). Microsatellite instability (MSI) was assessed by PCR and NGS (mSINGS).Results: Of primary adenocarcinomas and NEPC, 1...
November 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28753573/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#14
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28727698/high-prevalence-of-neuropathic-pain-component-in-patients-with-low-back-pain-evidence-from-meta-analysis
#15
Kapil Gudala, Dipika Bansal, Rambabu Vatte, Babita Ghai, Fabrizio Schifano, Chandrasehkar Boya
BACKGROUND: Low back pain (LBP) is a complex syndrome which includes a nociceptive (NcP) component, a neuropathic (NeP) component, or a mixture of components (mixed pain). The NeP component (NePC) in LBP is defined as the presence of NeP with or without an NcP. OBJECTIVE: This meta-analysis aimed at assessing the pooled prevalence of NePC in patients with LBP and at identifying the factors causing significant heterogeneity in reported prevalence. STUDY DESIGN: Meta-analysis...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28642484/mir-100-5p-inhibition-induces-apoptosis-in-dormant-prostate-cancer-cells-and-prevents-the-emergence-of-castration-resistant-prostate-cancer
#16
Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28506524/contemporary-incidence-and-cancer-control-outcomes-of-primary-neuroendocrine-prostate-cancer-a-seer-database-analysis
#17
Emanuele Zaffuto, Raisa Pompe, Marc Zanaty, Helen Davis Bondarenko, Sami-Ramzi Leyh-Bannurah, Marco Moschini, Paolo Dell'Oglio, Giorgio Gandaglia, Nicola Fossati, Armando Stabile, Kevin C Zorn, Francesco Montorsi, Alberto Briganti, Pierre I Karakiewicz
INTRODUCTION: Neuroendocrine carcinoma of the prostate (NEPC) is a rare entity. We aimed at providing contemporary data on incidence and survival figures of de-novo NEPC. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database, we identified 309 individuals with de-novo NEPC diagnosed between 2004 and 2013. We evaluated age-adjusted incidence rates over the study. Kaplan-Meier analyses assessed overall survival (OS) after stratification according to histologic subtype, metastatic status, and treatment...
April 13, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28482433/-clinical-characteristics-of-13-neuroendocrine-prostate-cancer-patients
#18
W H Zhang, T G Si, X L Yang, B Yang, C F Liu, H P Yu, W G Xing, Z Guo
Objective: To explore the radiological, pathological features and clinical characteristics of neuroendocrine prostate cancer patients(NEPC). Methods: The clinical characteristics and pathology data of 13 neuroendocrine prostate cancer patients treated in the Affiliated Hospital of Tianjin Medical University from January 2004 to January 2015 were analyzed retrospectively. Results: Of all 13 patients, three cases were primally diagnosed small cell cancer, and 10 cases were translated to neuroendocrine type from adenocarcinoma after endocrine therapy...
May 9, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28427194/alternative-rna-splicing-of-the-meaf6-gene-facilitates-neuroendocrine-prostate-cancer-progression
#19
Ahn R Lee, Yinan Li, Ning Xie, Martin E Gleave, Michael E Cox, Colin C Collins, Xuesen Dong
Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28361223/emerging-variants-of-castration-resistant-prostate-cancer
#20
REVIEW
Panagiotis J Vlachostergios, Loredana Puca, Himisha Beltran
Metastatic castration-resistant prostate cancer (CRPC) is associated with substantial clinical, pathologic, and molecular heterogeneity. Most tumors remain driven by androgen receptor (AR) signaling, which has clinical implications for patient selection for AR-directed approaches. However, histologic and clinical resistance phenotypes can emerge after AR inhibition, in which the tumors become less dependent on the AR. In this review, we discuss prostate cancer variants including neuroendocrine (NEPC) and aggressive variant (AVPC) prostate cancers and their clinical implications...
May 2017: Current Oncology Reports
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