Neuroendocrine Prostate Cancer (NEPC) Progressing From Conventional Prostatic Adenocarcinoma: Factors Associated With Time to Development of NEPC and Survival From NEPC Diagnosis—A Systematic Review and Pooled Analysis

Wang, Hai Tao; Yao, Yan; Li, Bao Guo; Tang, Yong; Chang, Jie; Zhang, Jiao

doi:10.1200/jco.2013.54.3553

Cited by 225 publications

(218 citation statements)

References 56 publications

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“…In addition, no treatment has demonstrated efficacy in extending the survival of NEPC patients. While median prostate adenocarcinoma survival is 125 months, median NEPC survival is only 7 months [18,19]. Hence, the phenotypic distinction between NEPC and adenocarcinoma is extremely important from a clinical perspective.…”

Section: Neuroendocrine Prostate Cancer: Clinical and Molecular Featuresmentioning

confidence: 99%

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

et al. 2016

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Neuroendocrine prostate cancer (NEPC) is the most lethal prostatic neoplasm.NEPC is thought to originate from the trans-differentiation of AR-positive adenocarcinoma cells. We have previously shown that an epigenetic/non-coding interactome (ENI) orchestrates cancer cells' plasticity, thereby allowing the emergence of metastatic, drugresistant neoplasms. The primary objective of this manuscript is to discuss evidence indicating that some components of the ENI (Polycomb genes, microRNAs) play a key role in NEPC initiation and progression. Long non-coding RNAs (lncRNAs) represent vast and largely unexplored component of the ENI. Their role in NEPC has not been investigated. We show preliminary evidence indicating that a lncRNA (MIAT) is selectively up-regulated in NEPCs and might interact with Polycomb genes. Our results indicate that lncRNAs can be exploited as new biomarkers and therapeutic targets for NEPC.Keywords: Neuroendocrine prostate cancer; MIAT; Long non-coding RNAs; Polycomb; Epigenetic/non-coding interactome; Trans-differentiation. Neuroendocrine Prostate Cancer: Clinical and Molecular FeaturesIn adult males, the prostate is a small acorn-shaped tissue with ductal-acinar histology surrounding the urethra at the base of the bladder. Its main function is to contribute secretory proteins to the seminal fluid [1]. The adult prostate is a pseudo-stratified epithelium composed of three main cell lineages (Fig.1, left panel): 1) secretory luminal cells are the predominant cell type; these cells express keratins (K8, K18), the androgen receptor (AR) and secretory proteins such as prostate-specific antigen (PSA) and prostatic specific acid phosphatase (PSAP);2) basal cells expressing K5 and K14 keratins and p63 are the second major cell type;3) neuroendocrine cells (NEC) expressing chromogranin A (CHGA), synaptophysin (SYP), and neuropeptides are scattered throughout the basal layer and comprise less than 1% of normal prostatic glandular epithelium [1][2][3].Prostate cancer (PCa) represents the second most frequently diagnosed neoplasm and is the sixth leading cause of cancer-related deaths in males worldwide [4,5]. In keeping with the composition of prostate epithelium, more than 95% of PCas are classified as adenocarcinomas, which show luminal phenotype and AR expression [6] (Fig.1, middle panel).Endogenous androgens, mainly produced by the testis, bind to the AR and fuel prostate adenocarcinoma proliferation [7]. For this reason, androgen-deprivation therapy (a.k.a. castration) is an effective therapeutic strategy for this disease. However, patients invariably relapse despite castrate androgen levels (castration-resistant PCa, CRPC) mainly via genetic and epigenetic alterations that facilitate ligand-independent AR activation, amplify the ARdependent signaling, or trigger different proliferative pathways [7]. CRPCs are characterized by substantially worse prognoses, but chemotherapeutics and newly approved hormonal treatments (e.g., Enzalutamide [8] and Abiraterone [9]) are still effective in p...

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Section: Neuroendocrine Prostate Cancer: Clinical and Molecular Featuresmentioning

confidence: 99%

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

et al. 2016

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“…In descending order of frequency, men with prostatic SCC most commonly present with voiding, neurologic (confusion, sensory/motor deficits), and/or constitutional symptoms [3]. SCC of the prostate arises in men with pre-existing adenocarcinoma who have received androgen deprivation in nearly half of cases [2,4,5]. This is believed to occur either due to adaptive dedifferentiation of malignant cells under the influence of ADT or the selective pressures of ADT favoring the proliferation of androgen receptor negative neuroendocrine cells [4].…”

Section: Discussionmentioning

confidence: 99%

Metastatic small cell carcinoma of the prostate in an octogenarian with significant response to first-line chemotherapy

Wood¹,

Adra²,

Liu³

et al. 2017

Hematol Med Oncol

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“…Neuroendocrine cells were identified as AR-negative cells responsible for both primary and acquired primary ADT and secondary hormonal therapies [52,60]. Interestingly, inside the West Coast Prostate Dream Team (WCDT) project, Small et al [61] performed biopsies from metastatic tissue in patients with CRPC resistant to abiraterone or enzalutamide, including genomic sequence and expression analysis.…”

Section: Mechanisms Of Resistance In Prostate Cancermentioning

confidence: 98%

New advances in genitourinary cancer: evidence gathered in 2014

Suárez

Puente

Gallardo³

et al. 2015

Cancer Metastasis Rev

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This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed.

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Neuroendocrine Prostate Cancer (NEPC) Progressing From Conventional Prostatic Adenocarcinoma: Factors Associated With Time to Development of NEPC and Survival From NEPC Diagnosis—A Systematic Review and Pooled Analysis

Cited by 225 publications

References 56 publications

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

Metastatic small cell carcinoma of the prostate in an octogenarian with significant response to first-line chemotherapy

New advances in genitourinary cancer: evidence gathered in 2014

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