scholarly journals Prominent response to platinum‐based chemotherapy in a patient with BRCA2 mutant‐neuroendocrine prostate cancer and MDM2 amplification

2021 ◽  
Author(s):  
Tatsuaki Daimon ◽  
Takeo Kosaka ◽  
Hiroshi Hongo ◽  
Eriko Aimono ◽  
Kohei Nakamura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neuroendocrine Prostate Cancer ◽  
Platinum Based Chemotherapy ◽  
Prominent Response ◽  
Mdm2 Amplification

scholarly journals Identification of Novel Diagnosis Biomarkers for Therapy-Related Neuroendocrine Prostate Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Cuijian Zhang ◽  
Jinqin Qian ◽  
Yucai Wu ◽  
Zhenpeng Zhu ◽  
Wei Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Characteristics ◽  
Expression Profiles ◽  
Prostate Adenocarcinoma ◽  
Diagnostic Tools ◽  
Receptor Interaction ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Platinum Based Chemotherapy

Background: Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks well-characterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing anti-androgen receptor therapy or switching to platinum-based chemotherapy.Methods: Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset.Results: A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively.Conclusion: The present study identified four specific novel biomarkers for therapy-related NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.

The prognostic biomarkers of the patients treated with platinum-based chemotherapy in treatment emergent or related neuroendocrine prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17576-e17576
Author(s):  
Takeo Kosaka ◽  
Hiroshi Hongo ◽  
Yota Yasumizu ◽  
Kazuhiro Matshumoto ◽  
Ryuichi Mizuno ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Prognostic Biomarkers ◽  
Monocyte Count ◽  
Chemotherapy Treatment ◽  
Visceral Metastasis ◽  
Risk Of Death ◽  
Neuroendocrine Prostate Cancer ◽  
Pathologic Features ◽  
Platinum Based Chemotherapy

e17576 Background: Treatment emergent or related neuroendocrine prostate cancer (tNEPC) is an aggressive subtype of prostate cancer in patients previously treated with androgen receptor pathway inhibitor (ARPI) as a mechanism of resistance. These patients are typically treated platinum-based chemotherapy using small cell lung cancer (SCLC). The clinical features of tNEPC are poorly defined. The aim of the present study was to investigate the prognostic biomarkers of the patients treated with platinum-based chemotherapy in tNEPC. Methods: We reviewed baseline, treatment and outcome data of 41 patients with tNEPC. Clinicopathological factors and laboratory data before administering the first cycle of platinum-based chemotherapy were collected to assess the prognostic factors for overall survival (OS). Definition of tNEPC were based on NEPC morphology on the basis of any current or prior tissue sample, development of liver metastases in the absent of PSA progression, or elevated serum neuron specific enolase (NSE). Results: Median PSA and NSE were 119.8 ng/ml and 18.2 ng/ml, respectively. Twenty-four patients had pathologic features of NEPC. NSE were elevated above the 32 patients. The median OS from the start of platinum-based chemotherapy treatment was 10 months. Univariate analysis revealed that LDH (p = 0.003), absolute monocyte count < 280 (p = 0.022), visceral metastasis (p = 0.014) prior to platinum-based chemotherapy were significantly associated with shorter OS. Multivariate analysis revealed that LDH (p = 0.047), absolute monocyte count < 280, (p = 0.012), visceral metastasis (p = 0.005) prior to platinum-based chemotherapy treatment were independent prognostic indicators for OS. Based on the relative risk of death, NEPC patients before platinum-based chemotherapy were divided into 3 risk groups: low, intermediate and high ( p< 0.001). Conclusions: Our findings provide new insights into the practical implication of NEPC. Our results might be to tailor the management of NEPC treated with platinum-based chemotherapy.

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 Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Siyuan Cheng ◽  
Shu Yang ◽  
Yingli Shi ◽  
Runhua Shi ◽  
Yunshin Yeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hox Genes ◽  
Human Cancer ◽  
Specific Expression ◽  
Hox Gene ◽  
Human Cancer Cell Lines ◽  
All Trans Retinoic Acid ◽  
Neuroendocrine Prostate Cancer ◽  
Hox Code ◽  
Specific Expression Pattern

AbstractHOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa. Also, our analysis showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue types, indicating that NEPCa tumors lose their prostate identities but do not gain new tissue identities. Additionally, using immunohistochemical staining, we evaluated the prostatic expression of HOXB13, the most prominently changed HOX gene in NEPCa. We found that HOXB13 was expressed in both benign prostatic tissues and AdPCa but its expression was reduced or lost in NEPCa. Furthermore, we treated PCa cells with all trans retinoic acid (ATRA) and found that the reduced HOXB13 expression can be reverted. This suggests that ATRA is a potential therapeutic agent for the treatment of NEPCa tumors by reversing them to a more treatable AdPCa.

scholarly journals CaV3.2 T-type calcium channels are involved in calcium-dependent secretion of neuroendocrine prostate cancer cells. VOLUME 283 (2008) PAGES 10162-10173

2008 ◽  
Vol 283 (28) ◽  
pp. 19872
Author(s):  
Florian Gackière ◽  
Gabriel Bidaux ◽  
Philippe Delcourt ◽  
Fabien Van Coppenolle ◽  
Maria Katsogiannou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Calcium Channels ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Calcium Dependent ◽  
Neuroendocrine Prostate Cancer

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 Morphologic, Molecular and Clinical Features of Aggressive Variant Prostate Cancer

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1073 ◽  
Author(s):  
Rodolfo Montironi ◽  
Alessia Cimadamore ◽  
Antonio Lopez-Beltran ◽  
Marina Scarpelli ◽  
Gaetano Aurilio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Final Diagnosis ◽  
Undifferentiated Carcinoma ◽  
Castration Resistant Prostate Cancer ◽  
Platinum Based Chemotherapy ◽  
Intermediate Part ◽  
Aggressive Variant

The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies.

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