scholarly journals Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Joanna Cyrta ◽  
Anke Augspach ◽  
Maria Rosaria De Filippo ◽  
Davide Prandi ◽  
Phillip Thienger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromatin Remodeling ◽  
Hormonal Treatment ◽  
Prostate Adenocarcinoma ◽  
Aggressive Disease ◽  
Chromatin Remodeling Complex ◽  
Large Patient ◽  
Neuroendocrine Prostate Cancer ◽  
Specific Factors

Abstract Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10–20% of these patients is lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify mSWI/SNF subunits that are deregulated in NEPC and demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease. We also show that SWI/SNF complexes interact with different lineage-specific factors in NEPC compared to prostate adenocarcinoma. These data point to a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may also be relevant for other solid tumors.

scholarly journals Role of Specialized Composition of SWI/SNF Complexes in Prostate Cancer Lineage Plasticity

2020 ◽  
Author(s):  
Joanna Cyrta ◽  
Anke Augspach ◽  
Maria Rosaria de Filippo ◽  
Davide Prandi ◽  
Phillip Thienger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromatin Remodeling ◽  
Hormonal Treatment ◽  
Prostate Adenocarcinoma ◽  
Aggressive Disease ◽  
Chromatin Remodeling Complex ◽  
Large Patient ◽  
Neuroendocrine Prostate Cancer ◽  
Specific Factors

AbstractAdvanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in ∼10% of these patients is through lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify mSWI/SNF subunits that are deregulated in NEPC and demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease. We also show that SWI/SNF complexes interact with different lineage-specific factors in NEPC compared to prostate adenocarcinoma. These data suggest a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may be relevant for other solid tumors.

scholarly journals Neuroendocrine Differentiation of Prostate Cancer—An Intriguing Example of Tumor Evolution at Play

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1405 ◽  
Author(s):  
Patel ◽  
Chugh ◽  
Tripathi
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Neuroendocrine Differentiation ◽  
Prostate Adenocarcinoma ◽  
Tumor Evolution ◽  
Aggressive Form ◽  
Neuroendocrine Prostate Cancer ◽  
Key Driver ◽  
New Perspective

Our understanding of neuroendocrine prostate cancer (NEPC) has assumed a new perspective in light of the recent advances in research. Although classical NEPC is rarely seen in the clinic, focal neuroendocrine trans-differentiation of prostate adenocarcinoma occurs in about 30% of advanced prostate cancer (PCa) cases, and represents a therapeutic challenge. Even though our knowledge of the mechanisms that mediate neuroendocrine differentiation (NED) is still evolving, the role of androgen deprivation therapy (ADT) as a key driver of this phenomenon is increasingly becoming evident. In this review, we discuss the molecular, cellular, and therapeutic mediators of NED, and emphasize the role of the tumor microenvironment (TME) in orchestrating the phenotype. Understanding the role of the TME in mediating NED could provide us with valuable insights into the plasticity associated with the phenotype, and reveal potential therapeutic targets against this aggressive form of PCa.

scholarly journals Critical role of Brg1 member of the SWI/SNF chromatin remodeling complex during neurogenesis and neural crest induction in zebrafish

2006 ◽  
Vol 235 (10) ◽  
pp. 2722-2735 ◽  
Author(s):  
Binnur Eroglu ◽  
Guanghu Wang ◽  
Naxin Tu ◽  
Xutong Sun ◽  
Nahid F. Mivechi
Keyword(s):  
Neural Crest ◽  
Chromatin Remodeling ◽  
Critical Role ◽  
Chromatin Remodeling Complex

scholarly journals Circulating tumor cell heterogeneity in neuroendocrine prostate cancer by single cell copy number analysis

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Vincenza Conteduca ◽  
Sheng-Yu Ku ◽  
Luisa Fernandez ◽  
Angel Dago-Rodriquez ◽  
Jerry Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Cell ◽  
De Novo ◽  
Genomic Analysis ◽  
Treatment Resistance ◽  
Circulating Tumor Cell ◽  
Prostate Adenocarcinoma ◽  
Neuroendocrine Prostate Cancer ◽  
Patient Heterogeneity ◽  
Tumor Cell Heterogeneity

AbstractNeuroendocrine prostate cancer is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. The combined loss of tumor suppressors RB1, TP53, and PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and preclinical studies support a trans-differentiation process, whereby NEPC arises clonally from a prostate adenocarcinoma precursor during the course of treatment resistance. Here we highlight a case of NEPC with significant intra-patient heterogeneity observed across metastases. We further demonstrate how single-cell genomic analysis of circulating tumor cells combined with a phenotypic evaluation of cellular diversity can be considered as a window into tumor heterogeneity in patients with advanced prostate cancer.

scholarly journals The Role of Hormonal Treatment in Prostate Cancer

2007 ◽  
pp. 211-237 ◽  
Author(s):  
Stephan H. Flüchter ◽  
Ralf Weiser ◽  
Christoph Gamper
Keyword(s):  
Prostate Cancer ◽  
Hormonal Treatment

scholarly journals The role of the SWI/SNF chromatin remodeling complex in pancreatic ductal adenocarcinoma

2020 ◽  
Author(s):  
Motoyuki Tsuda ◽  
Akihisa Fukuda ◽  
Munenori Kawai ◽  
Osamu Araki ◽  
Hiroshi Seno
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Chromatin Remodeling ◽  
Ductal Adenocarcinoma ◽  
Chromatin Remodeling Complex

The Role of Hormonal Treatment in Prostate Cancer

2017 ◽  
pp. 333-349
Author(s):  
Pervin Hurmuz ◽  
Fadıl Akyol ◽  
Melis Gultekin ◽  
Gozde Yazici ◽  
Sezin Yuce Sari ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormonal Treatment

Abstract 5191: Functional role of EZH2 in neuroendocrine prostate cancer

2019 ◽  
Author(s):  
Md Imtiaz Khalil ◽  
Shu Yang ◽  
Anthony Blankenship ◽  
Zachary Connelly ◽  
Xiuping Yu
Keyword(s):  
Prostate Cancer ◽  
Functional Role ◽  
Neuroendocrine Prostate Cancer

Determining issues of importance for patients with prostate cancer: Results of a web-based study in 2,128 patients with prostate cancer for the development of a quality of life (QL) instrument, the prostate cancer symptom scale (PCSS)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5138-5138
Author(s):  
R. J. Gralla ◽  
P. J. Hollen ◽  
B. J. Davis ◽  
J. A. Petersen ◽  
R. Thompson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Content Validity ◽  
Strong Support ◽  
Hormonal Treatment ◽  
Current Treatment ◽  
Computer Assisted ◽  
Symptom Scale ◽  
Web Based ◽  
Large Patient ◽  
Patient Reported

5138 Background: Identifying key issues for patients with malignancy is central to assessing QL and patient reported outcomes. This aids in evaluating the effectiveness of treatment programs for those with the disease. The immediate aim of this study was to determine content validity using a large patient panel for the PCSS, a QL measure for patients with prostate cancer. The PCSS also uses an inexpensive hand-held pocket PC to enhance feasibility. The PCSS concept is based on the LCSS (a validated lung cancer instrument). Methods: We used the established patient base of the web-based NexCura patient information resource to survey registered patients with prostate cancer. Demographic stratifications included stage of disease, prior radical prostatectomy, and current treatment (none, hormonal, non-hormonal). 2,128 patients completed the anonymous web-conducted survey, performed over a 3-day period. Patients were asked to rank 18 issues on a 5-point scale assessing the importance of each item. Issues included general, prostate-specific, psychosocial and summative items. Results: The 10 highest (and 2 lowest) ranked items are seen in the table ; results are described by the percent of patients choosing the top category (very important) and the top 2 rating categories of importance. Ratings by disease subsets (such as NED or metastatic disease; hormonal or non-hormonal treatment) were quite similar to results found for the whole group, as listed in the table . Conclusions: These results represent the largest survey of patient concerns in prostate cancer and support using computer-assisted survey technology to assess such information in all malignancies to obtain patient input rapidly from large patient samples. Strong support for content validity for the PCSS was obtained. [Table: see text] No significant financial relationships to disclose.

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