scholarly journals Imaging of Neuroendocrine Prostatic Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5765
Author(s):  
Ahmed Taher ◽  
Corey T. Jensen ◽  
Sireesha Yedururi ◽  
Devaki Shilpa Surasi ◽  
Silvana C. Faria ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Poor Prognosis ◽  
Prostatic Carcinoma ◽  
De Novo ◽  
Treatment Resistance ◽  
Metastatic Potential ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Aggressive Subtype

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that typically has a high metastatic potential and poor prognosis in comparison to the adenocarcinoma subtype. Although it can arise de novo, NEPC much more commonly occurs as a mechanism of treatment resistance during therapy for conventional prostatic adenocarcinoma, the latter is also termed as castration-resistant prostate cancer (CRPC). The incidence of NEPC increases after hormonal therapy and they represent a challenge, both in the radiological and pathological diagnosis, as well as in the clinical management. This article provides a comprehensive imaging review of prostatic neuroendocrine tumors.

scholarly journals Loss of EHF facilitates the development of treatment-induced neuroendocrine prostate cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhi Long ◽  
Liang Deng ◽  
Chao Li ◽  
Qiangrong He ◽  
Yao He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcriptional Repression ◽  
Critical Role ◽  
Histone H3 ◽  
Neuroendocrine Differentiation ◽  
Cell Models ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Aggressive Subtype

AbstractThe rising of a highly aggressive subtype of castration-resistant prostate cancer (CRPC) named treatment-induced neuroendocrine prostate cancer (t-NEPC) after androgen deprivation therapy (ADT) is well known for its features of the neuroendocrine differentiation (NED) and androgen receptor (AR) independence. However, t-NEPC is still largely unknown. Here, we found that EHF is notably depressed in t-NEPC tumors, patient-derived xenografts, transgenic mice, and cell models. Results from cell lines uncovered that ADT represses EHF expression, which is required for the ADT-induced NED. Mechanism dissection revealed that ADT decreases the EHF transcription via relieving the AR binding to different androgen-responsive elements, which then promotes the expression and enzymatic activity of enhancer of zeste homolog 2 (EZH2), consequently catalyzing tri-methylation lysine 27 of histone H3 for transcriptional repression of its downstream genes to promote the NED. Furthermore, preclinical studies from cell and mice models proved that recovery of EHF expression or using EZH2 inhibitor can attenuate aggressive properties of CRPC cells, hinder the progression of t-NEPC, and promote the response of CPRC cells to enzalutamide. Together, we elucidate that the ADT/AR/EHF/EZH2 signaling is required for the ADT-enhanced NED and plays a critical role in the progression of t-NEPC.

scholarly journals The Crosstalk of Long Non-Coding RNA and MicroRNA in Castration-Resistant and Neuroendocrine Prostate Cancer: Their Interaction and Clinical Importance

2021 ◽  
Vol 23 (1) ◽  
pp. 392
Author(s):  
Che-Yuan Hu ◽  
Kuan-Yu Wu ◽  
Tsung-Yen Lin ◽  
Chien-Chin Chen
Keyword(s):  
Prostate Cancer ◽  
Median Survival ◽  
De Novo ◽  
Neuroendocrine Differentiation ◽  
Cancer Development ◽  
Current Evidence ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Epigenetic Regulators

Prostate cancer is featured by its heterogeneous nature, which indicates a different prognosis. Castration-resistant prostate cancer (CRPC) is a hallmark of the treatment-refractory stage, and the median survival of patients is only within two years. Neuroendocrine prostate cancer (NEPC) is an aggressive variant that arises from de novo presentation of small cell carcinoma or treatment-related transformation with a median survival of 1–2 years from the time of diagnosis. The epigenetic regulators, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been proven involved in multiple pathologic mechanisms of CRPC and NEPC. LncRNAs can act as competing endogenous RNAs to sponge miRNAs that would inhibit the expression of their targets. After that, miRNAs interact with the 3’ untranslated region (UTR) of target mRNAs to repress the step of translation. These interactions may modulate gene expression and influence cancer development and progression. Otherwise, epigenetic regulators and genetic mutation also promote neuroendocrine differentiation and cancer stem-like cell formation. This step may induce neuroendocrine prostate cancer development. This review aims to provide an integrated, synthesized overview under current evidence to elucidate the crosstalk of lncRNAs with miRNAs and their influence on castration resistance or neuroendocrine differentiation of prostate cancer. Notably, we also discuss the mechanisms of lncRNA–miRNA interaction in androgen receptor-independent prostate cancer, such as growth factors, oncogenic signaling pathways, cell cycle dysregulation, and cytokines or other transmembrane proteins. Conclusively, we underscore the potential of these communications as potential therapeutic targets in the future.

scholarly journals Molecular and Functional Links between Neurodevelopmental Processes and Treatment-Induced Neuroendocrine Plasticity in Prostate Cancer Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 692
Author(s):  
Roosa Kaarijärvi ◽  
Heidi Kaljunen ◽  
Kirsi Ketola
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Treatment Resistance ◽  
Research Field ◽  
Phenotypic Change ◽  
Prostate Cancer Progression ◽  
Castration Resistant Prostate Cancer ◽  
Treatment Resistant ◽  
Molecular Features ◽  
Neuroendocrine Prostate Cancer

Neuroendocrine plasticity and treatment-induced neuroendocrine phenotypes have recently been proposed as important resistance mechanisms underlying prostate cancer progression. Treatment-induced neuroendocrine prostate cancer (t-NEPC) is highly aggressive subtype of castration-resistant prostate cancer which develops for one fifth of patients under prolonged androgen deprivation. In recent years, understanding of molecular features and phenotypic changes in neuroendocrine plasticity has been grown. However, there are still fundamental questions to be answered in this emerging research field, for example, why and how do the prostate cancer treatment-resistant cells acquire neuron-like phenotype. The advantages of the phenotypic change and the role of tumor microenvironment in controlling cellular plasticity and in the emergence of treatment-resistant aggressive forms of prostate cancer is mostly unknown. Here, we discuss the molecular and functional links between neurodevelopmental processes and treatment-induced neuroendocrine plasticity in prostate cancer progression and treatment resistance. We provide an overview of the emergence of neurite-like cells in neuroendocrine prostate cancer cells and whether the reported t-NEPC pathways and proteins relate to neurodevelopmental processes like neurogenesis and axonogenesis during the development of treatment resistance. We also discuss emerging novel therapeutic targets modulating neuroendocrine plasticity.

scholarly journals Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divya Bhagirath ◽  
Michael Liston ◽  
Theresa Akoto ◽  
Byron Lui ◽  
Barbara A. Bensing ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Neuroendocrine Differentiation ◽  
Extracellular Vesicle ◽  
Machine Learning Algorithms ◽  
Castration Resistant Prostate Cancer ◽  
Cellular Models ◽  
Non Invasive ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer

AbstractNeuroendocrine prostate cancer (NEPC), a highly aggressive variant of castration-resistant prostate cancer (CRPC), often emerges upon treatment with androgen pathway inhibitors, via neuroendocrine differentiation. Currently, NEPC diagnosis is challenging as available markers are not sufficiently specific. Our objective was to identify novel, extracellular vesicles (EV)-based biomarkers for diagnosing NEPC. Towards this, we performed small RNA next generation sequencing in serum EVs isolated from a cohort of CRPC patients with adenocarcinoma characteristics (CRPC-Adeno) vs CRPC-NE and identified significant dysregulation of 182 known and 4 novel miRNAs. We employed machine learning algorithms to develop an ‘EV-miRNA classifier’ that could robustly stratify ‘CRPC-NE’ from ‘CRPC-Adeno’. Examination of protein repertoire of exosomes from NEPC cellular models by mass spectrometry identified thrombospondin 1 (TSP1) as a specific biomarker. In view of our results, we propose that a miRNA panel and TSP1 can be used as novel, non-invasive tools to identify NEPC and guide treatment decisions. In conclusion, our study identifies for the first time, novel non-invasive exosomal/extracellular vesicle based biomarkers for detecting neuroendocrine differentiation in advanced castration resistant prostate cancer patients with important translational implications in clinical management of these patients that is currently extremely challenging.

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 Dietary Tomato or Lycopene Do Not Reduce Castration-Resistant Prostate Cancer Progression in a Murine Model

2020 ◽  
Vol 150 (7) ◽  
pp. 1808-1817
Author(s):  
Joe L Rowles ◽  
Joshua W Smith ◽  
Catherine C Applegate ◽  
Rita J Miller ◽  
Matthew A Wallig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Control Diet ◽  
Tumor Detection ◽  
Castration Resistant Prostate Cancer ◽  
Tumor Weight ◽  
Castration Resistant ◽  
Mouse Prostate ◽  
Tomato Powder ◽  
Tramp Mice

ABSTRACT Background Dietary tomato products or lycopene protect against prostate carcinogenesis, but their impact on the emergence of castration-resistant prostate cancer (CRPC) is unknown. Objective We hypothesized that tomato or lycopene products would reduce the emergence of CRPC. Methods Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were castrated at 12–13 wk and the emergence of CRPC was monitored by ultrasound in each study. In Study 1, TRAMP mice (n = 80) were weaned onto an AIN-93G-based control diet (Con-L, n = 28), a 10% tomato powder diet (TP-L, 10% lyophilized w/w, n = 26), or a control diet followed by a tomato powder diet after castration (TP-Int1, n = 26). In Study 2, TRAMP mice (n = 85) were randomized onto a control diet with placebo beadlets (Con-Int, n = 29), a tomato diet with placebo beadlets (TP-Int2, n = 29), or a control diet with lycopene beadlets (Lyc-Int, n = 27) following castration (aged 12 wk). Tumor incidence and growth were monitored by ultrasound beginning at an age of 10 wk. Mice were euthanized 4 wk after tumor detection or aged 30 wk if no tumor was detected. Tissue weights were compared by ANOVA followed by Dunnett's test. Tumor volumes were compared using generalized linear mixed model regression. Results Ultrasound estimates for the in vivo tumor volume were strongly correlated with tumor weight at necropsy (R2 = 0.75 and 0.94, P <0.001 for both Studies 1 and 2, respectively). Dietary treatments after castration did not significantly impact cancer incidence, time to tumor detection, or final tumor weight. Conclusions In contrast to studies of de novo carcinogenesis in multiple preclinical models, tomato components had no significant impact on the emergence of CRPC in the TRAMP model. It is possible that specific mutant subclones of prostate cancer may continue to show some antiproliferative response to tomato components, but further studies are needed to confirm this.

Phase III SYNERGY trial: Docetaxel +/- custirsen and overall survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and poor prognosis.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 5009-5009 ◽  
Author(s):  
Kim N. Chi ◽  
Celestia S. Higano ◽  
Brent A. Blumenstein ◽  
James Andrew Reeves ◽  
Susan Feyerabend ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Prevalence of oligoprogressive, metastatic castration-resistant prostate cancer (mCRPC) amenable to stereotactic ablative radiotherapy (SABR) in men undergoing abiraterone acetate (AA) therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16509-e16509
Author(s):  
Erica McDonald ◽  
Sierra Cheng ◽  
Vanessa Sarah Arciero ◽  
Ronak Saluja ◽  
Katherine A. Zukotynski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
De Novo ◽  
Metastatic Tumor ◽  
Clinical Situation ◽  
Abiraterone Acetate ◽  
Stereotactic Ablative Radiotherapy ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Metastatic Lesions

e16509 Background: SABR is increasingly used for treating men with oligometastatic prostate cancer, a state between loco-regional and widespread metastatic disease that exists de novo, presents as oligorecurrence, is treatment-induced, or occurs as oligoprogression. The latter is a clinical situation where a limited number of metastatic tumor sites progress (usually defined as ≤3-5), while all other metastases are controlled by a given systemic therapy. The frequency of oligoprogression amenable to SABR is unknown. Methods: Thus, in a retrospective chart analysis we studied the progression pattern of 35 men with chemotherapy-naïve mCRPC undergoing AA therapy, and of 20 men undergoing AA therapy after docetaxel chemotherapy. Applying RECIST1.1 and/or PCWG2 criteria, patients (pts) were considered SABR candidates if they radiologically progressed in ≤5 distinct metastatic locations, while all other sites were stable or responding. Results: In chemotherapy-naïve men, pre-AA metastatic lesions were located in bone (94%), lymph nodes (49%), lungs (17%) and liver (3%), whereas progression during AA therapy occurred in bone (89%), lymph nodes (49%), lungs (14%) and liver (9%). 12 pts (34%) met the criteria of oligoprogression with a median of 2 progressive lesions/pt (range 1-5). 8 pts presented with bone progression only, 3 with nodal progression, and 1 pt with combined bone/nodal progression. Post-docetaxel pts had pre-AA metastatic lesions located in bone (75%), lymph nodes (35%), lungs (5%) and liver (5%). Progression during AA therapy occurred in bone (80%), lymph nodes (75%), lungs (20%) and liver (5%). Only 1 pt met oligoprogression criteria with a single progressive bone metastasis. Conclusions: A sizeable number of men with chemotherapy-naïve mCRPC progressing during AA therapy might be considered for SABR. By contrast, progression of post-docetaxel mCRPC treated with AA is typically widespread. Further efforts are needed to identify criteria for oligoprogressive pts most suitable for SABR with sustained benefit versus men that may progress rapidly with widespread metastases following radiotherapy.

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