Keywords late-stage neuroendocrine pros...

late-stage neuroendocrine prostate cancer
Jing Wang, Ling-Fan Xu, Cheng Liu, Tao Huang, Chao-Zhao Liang, Yi-Dong Fan
Although localized prostate cancer (PCa) can be cured by prostatectomy and radiotherapy, the development of effective therapeutic approaches for advanced prostate cancer, including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), is lagging far behind. Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need. Here, we report that apolipoprotein A-I (ApoA-I), the major component of high-density lipoprotein (HDL), is upregulated in PCa based on both bioinformatics and experimental evidence...
February 12, 2021: Asian Journal of Andrology
Sakshi Goel, Vipul Bhatia, Tanay Biswas, Bushra Ateeq
Conrad Waddington's theory of epigenetic landscape epitomize the process of cell fate and cellular decision-making during development. Wherein the epigenetic code maintains patterns of gene expression in pluripotent and differentiated cellular states during embryonic development and differentiation. Over the years disruption or reprogramming of the epigenetic landscape has been extensively studied in the course of cancer progression. Cellular dedifferentiation being a key hallmark of cancer allow us to take cues from the biological processes involving epigenetic reprogramming in development such as the cellular differentiation and morphogenesis...
February 2, 2021: Seminars in Cancer Biology
Yasutaka Yamada, Himisha Beltran
PURPOSE OF REVIEW: Neuroendocrine prostate cancer (NEPC) is an aggressive histologic subtype of prostate cancer that most commonly arises in later stages of prostate cancer as a mechanism of treatment resistance. The poor prognosis of NEPC is attributed in part to late diagnosis and a lack of effective therapeutic agents. Here, we review the clinical and molecular features of NEPC based on recent studies and outline future strategies and directions. RECENT FINDINGS: NEPC can arise "de novo" but most commonly develops as a result of lineage plasticity whereby prostate cancer cells adopt alternative lineage programs as a means to bypass therapy...
January 12, 2021: Current Oncology Reports
Katharina Kessel, Robert Seifert, Matthias Weckesser, Wolfgang Roll, Verena Humberg, Katrin Schlack, Martin Bögemann, Christof Bernemann, Kambiz Rahbar
Rationale: Lu-177-PSMA-617 radioligand therapy (RLT) is currently under approval for treatment of metastatic castration resistant prostate cancer (mCRPC) patients with late stage disease. However, previous studies demonstrated both heterogeneity of prostate specific membrane antigen (PSMA) expression, as well as response to PSMA treatment among mCRPC patients. Thus, there is an unmet need for identifying predictive parametres prior or under PSMA-RLT treatment. We therefore aimed to correlate several clinical and molecular parameters with response to PSMA treatment in a cohort of mCRPC patients undergoing PSMA RLT followed by a detailed analysis of promising candidates...
2020: Theranostics
Vasiliki Tzelepi, Souzana Logotheti, Eleni Efstathiou, Patricia Troncoso, Ana Aparicio, Minas Sakellakis, Anh Hoang, Petros Perimenis, Maria Melachrinou, Christopher Logothetis, Vasiliki Zolota
DNA methyltransferases (DNMTs) regulate gene expression by methylating cytosine residues within CpG dinucleotides. Aberrant methylation patterns have been shown in a variety of human tumours including prostate cancer. However, the expression of DNMTs in clinical samples across the spectrum of prostate cancer progression has not been studied before. Tissue microarrays were constructed from the prostatectomy specimens of 309 patients across the spectrum of prostate cancer progression: hormone-naïve low-grade prostate cancer (n=49), hormone-naïve high-grade prostate cancer (n=151), hormonally treated high-grade prostate cancer (n=65), and castrate-resistant prostate cancer (CRPC) including neuroendocrine carcinoma (n=44)...
December 18, 2019: Pathology
Sharjeel Usmani, Marina Orevi, Antonella Stefanelli, Alberto Zaniboni, Ofer Nathan Gofrit, Claudio Bnà, Sonia Illuminati, Giulia Lojacono, Silvia Noventa, Giordano Savelli
BACKGROUND: Androgen Deprivation Therapy (ADT) is the primary treatment for patients suffering from relapsing or advanced prostate cancer (PC). Hormone therapy generally guarantees adequate clinical control of the disease for some years, even in those patients affected by widespread skeletal and soft tissue metastases. Despite ADT, however, most patients treated with hormones eventually progress to castration-resistant prostate cancer (CRPC), for which there are no effective treatments...
June 2019: Critical Reviews in Oncology/hematology
Galina Gritsina, Wei-Qiang Gao, Jindan Yu
Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes...
May 2019: Asian Journal of Andrology
Cristina Quicios-Dorado, Eduardo Bolufer-Moragues, Carmen Gomis-Goti, Ramiro Cabello-Benavente, Pablo Javier Cannata-Ortiz, Carmen González-Enguita
Castration resistant prostate cancer (CRPC) is characterized by an important molecular, pathological and clinical heterogeneity. Although most of them present androgen receptor (AR) signal dependence, there are independent phenotypes. Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype with adverse prognosis due to late diagnosis, heterogeneous clinical features and lack of effective systemic treatments. Platinum based chemotherapy is the standard treatment, presenting short limited responses...
September 2018: Archivos Españoles de Urología
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment-induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate-resistant prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and, for most patients, result in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
June 1, 2018: GigaScience
Justin Lack, Marc Gillard, Maggie Cam, Gladell P Paner, David J VanderWeele
BACKGROUND: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. METHODS: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each...
February 23, 2017: Journal of Translational Medicine
H Choe, A Sboner, H Beltran, D Nanus, S T Tagawa
INTRODUCTION: Neuroendocrine prostate cancer (NEPC) is an aggressive late-stage variant of PC that is often androgen-receptor negative. Most clinicians believe the VTE rate with NEPC is higher than with standard metastatic castration-resistant PC (mCRPC), but NEPC tends to present with bulkier visceral disease and include platinum chemotherapy unlike standard PC. In many solid tumors, a more aggressive phenotype correlates with increased VTE risk and elevated expression of coagulation factors...
April 2016: Thrombosis Research
John K Lee, John W Phillips, Bryan A Smith, Jung Wook Park, Tanya Stoyanova, Erin F McCaffrey, Robert Baertsch, Artem Sokolov, Justin G Meyerowitz, Colleen Mathis, Donghui Cheng, Joshua M Stuart, Kevan M Shokat, W Clay Gustafson, Jiaoti Huang, Owen N Witte
MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone...
April 11, 2016: Cancer Cell
Daniel H Shevrin
In spite of the development of new treatments for late stage prostate cancer, significant challenges persist to match individuals with effective targeted therapies. Genomic classification using high-throughput sequencing technologies has the potential to achieve this goal and make precision medicine a reality in the management of men with castrate-resistant prostate cancer. This chapter reviews some of the most recent studies that have resulted in significant progress in determining the landscape of somatic genomic alterations in this cohort and, more importantly, have provided clinically actionable information that could guide treatment decisions...
July 2016: Asian Journal of Andrology
Mark P Labrecque, Mandeep K Takhar, Rebecca Nason, Stephanie Santacruz, Kevin J Tam, Shabnam Massah, Anne Haegert, Robert H Bell, Manuel Altamirano-Dimas, Colin C Collins, Frank J S Lee, Gratien G Prefontaine, Michael E Cox, Timothy V Beischlag
Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1...
April 26, 2016: Oncotarget
Bryan A Smith, Artem Sokolov, Vladislav Uzunangelov, Robert Baertsch, Yulia Newton, Kiley Graim, Colleen Mathis, Donghui Cheng, Joshua M Stuart, Owen N Witte
Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer...
November 24, 2015: Proceedings of the National Academy of Sciences of the United States of America
Panagiotis J Vlachostergios, Christos N Papandreou
Neuroendocrine prostate carcinoma, either co-present with the local adenocarcinoma disease or as a result of transdifferentiation later in time, was described as one major process of emerging resistance to androgen deprivation therapies, and at the clinical level it is consistent with the development of rapidly progressive visceral disease, often in the absence of elevated serum prostate-specific antigen level. Until present, platinum-based chemotherapy has been the only treatment modality, able to produce a fair amount of responses but of short duration...
2015: Frontiers in Oncology
Juan Miguel Mosquera, Himisha Beltran, Kyung Park, Theresa Y MacDonald, Brian D Robinson, Scott T Tagawa, Sven Perner, Tarek A Bismar, Andreas Erbersdobler, Rajiv Dhir, Joel B Nelson, David M Nanus, Mark A Rubin
Neuroendocrine prostate cancer (NEPC), also referred to as anaplastic prostate cancer, is a lethal tumor that most commonly arises in late stages of prostate adenocarcinoma (PCA) with predilection to metastasize to visceral organs. In the current study, we explore for evidence that Aurora kinase A (AURKA) and N-myc (MYCN) gene abnormalities are harbingers of treatment-related NEPC (t-NEPC). We studied primary prostate tissue from 15 hormone naïve PCAs, 51 castration-resistant prostate cancers, and 15 metastatic tumors from 72 patients at different stages of disease progression to t-NEPC, some with multiple specimens...
January 2013: Neoplasia: An International Journal for Oncology Research
Teresa A Almeida, Yurena Rodriguez, Mariano Hernández, Ricardo Reyes, Aixa R Bello
Neurotensin is a neuroendocrine peptide acting as a trophic factor in a variety of cells in vivo but it can also function as an autocrine growth factor in human prostate cancer cells in vitro. In addition, the high-affinity G protein-coupled NT receptor (NTS1) is overexpressed in prostate cancer cell lines. Increasing evidence argues for a direct correlation between specific alternative splice variants and cancer. We detected four splice variants of the NTS1 receptor in human prostate cancer cell lines. These isoforms include one or more exons skipping as well as an alternative 5' splice donor site and are expressed in the late-stage androgen independent prostate cancer cell lines PC3 and DU145, but not in the early-stage androgen-sensitive LNCaP or in normal prostate tissue, which only express the normal transcript...
February 2010: Peptides
Tatyana Isayeva, Diptiman Chanda, Lisa Kallman, Isam-Eldin A Eltoum, Selvarangan Ponnazhagan
Antiangiogenic therapy is a promising alternative for prostate cancer growth and metastasis and holds great promise as an adjuvant therapy. The present study evaluated the potential of stable expression of angiostatin and endostatin before the onset of neoplasia and during the early and late stages of prostate cancer progression in transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Groups of 5-, 10-, and 18-week-old male TRAMP mice received recombinant adeno-associated virus-6 encoding mouse endostatin plus angiostatin (E+A) by i...
June 15, 2007: Cancer Research
G P Amorino, P D Deeble, S J Parsons
Neuroendocrine (NE)-like cells are hypothesized to contribute to the progression of prostate cancer by producing factors that enhance the growth, survival or metastatic capabilities of surrounding tumor cells. Many of the factors known to be secreted by NE-like cells, such as neurotensin (NT), parathyroid hormone-related peptide, serotonin, bombesin, etc., are agonists for G-protein-coupled receptors, but the signaling pathways activated by these agonists in prostate tumor cells are not fully defined. Identification of such pathways could provide insights into novel methods of treating late-stage disease...
February 1, 2007: Oncogene
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