Prostate cancer (PCa) is the most common cause of cancer death among African men. The presence of tumor-specific variations in cell-free DNA (cfDNA), such as mutations, microsatellite instability, and DNA methylation, has been explored as a source of biomarkers for cancer diagnosis. In this study, we investigated the diagnostic role of cfDNA among South African PCa patients.
View Article and Find Full Text PDFProstate cancer (PCa) is the most common cause of cancer death among African men. The analysis of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) can be utilized as a non-invasive tool for the diagnosis of PCa. In this study, we used small RNA sequencing to profile miRNAs cargo in plasma EVs from South African PCa patients.
View Article and Find Full Text PDFProstate cancer (PCa) is the most common malignancy and the second leading cause of cancer-related death amongst men in the United States. Neuroendocrine prostate cancer (NEPC) can either arise de novo or emerge as a consequence of therapy. De novo NEPC is rare, with an incidence of <2% of all PCa cases.
View Article and Find Full Text PDFBackground: Oncogenic transformation alters intracellular metabolism and contributes to the growth of malignant cells. Metabolomics, or the study of small molecules, can reveal insight about cancer progression that other biomarker studies cannot. Number of metabolites involved in this process have been in spotlight for cancer detection, monitoring, and therapy.
View Article and Find Full Text PDFThe multi-kinase inhibitor sorafenib is a primary treatment modality for advanced-stage hepatocellular carcinoma (HCC). However, the therapeutic benefits are short-lived due to innate and acquired resistance. Here, we examined how HCC cells respond to sorafenib and adapt to continuous and prolonged exposure to the drug.
View Article and Find Full Text PDFBackground: Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. The study of PCa in the South African population represents an opportunity for biomedical research due to the high prevalence of aggressive PCa. While inflammation is known to play a significant role in PCa progression, its association with tumor stage in populations of African descent has not been explored in detail.
View Article and Find Full Text PDFThe TMPRSS2-ERG gene fusion is the most frequent alteration observed in human prostate cancer. However, its role in disease progression is still unclear. In this study, we uncover an important mechanism promoting ERG oncogenic activity.
View Article and Find Full Text PDFDriver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that mutually exclusive prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are synthetic sick. At the molecular level, the incompatible cancer pathways are driven by opposing functions in SPOP.
View Article and Find Full Text PDFExtracellular vesicles (EVs) are relevant means for transferring signals across cells and facilitate propagation of oncogenic stimuli promoting disease evolution and metastatic spread in cancer patients. Here, we investigated the release of miR-424 in circulating small EVs or exosomes from prostate cancer patients and assessed the functional implications in multiple experimental models. We found higher frequency of circulating miR-424 positive EVs in patients with metastatic prostate cancer compared to patients with primary tumors and BPH.
View Article and Find Full Text PDFCancers (Basel)
October 2020
Cancers (Basel)
January 2020
In this study, we extracted prostate cell-specific gene sets (metagenes) to define the epithelial differentiation status of prostate cancers and, using a deconvolution-based strategy, interrogated thousands of primary and metastatic tumors in public gene profiling datasets. We identified a subgroup of primary prostate tumors with low luminal epithelial enrichment (LumE). LumE tumors were associated with higher Gleason score and mutational burden, reduced relapse-free and overall survival, and were more likely to progress to castration-resistant prostate cancer (CRPC).
View Article and Find Full Text PDFThe emergence of therapy-resistant cancer stem cells (CSCs) limit the efficacy of prostate cancer treatment. Using genetic knockdown and chemical inhibitors, we demonstrate the critical role of Bromodomain Containing 4 (BRD4) in promoting mitochondrial fission and sustaining CSC expansion. These findings provide a new paradigm for developing novel treatment strategies for prostate cancer.
View Article and Find Full Text PDFLiquid biopsy technologies have the potential to transform cancer patient management as it offers non-invasive diagnosis and real-time monitoring of disease progression and treatment responses. The use of liquid biopsy for non-invasive cancer diagnosis can have pivotal importance for the African continent where access to medical infrastructures is limited, as it eliminates the need for surgical biopsies. To apply liquid biopsy technologies in the African setting, the influence of environmental and population genetic factors must be known.
View Article and Find Full Text PDFBackground: Chemotherapy is the treatment of choice for metastatic castration-resistant prostate cancer (mCRPC) nonresponsive to androgen receptor-targeted therapies. Nevertheless, the impact of chemotherapy on patient survival is limited and clinical outcome remain dismal. Bromodomain and extraterminal inhibitors (BETis) are attractive therapeutic agents and currently in clinical trials to be tested for their efficacy in prostate cancer patients.
View Article and Find Full Text PDFBackground: The TMPRSS2-ERG gene fusion is the most frequent genetic rearrangement in prostate cancers and results in broad transcriptional reprogramming and major phenotypic changes. Interaction and cooperation of ERG and SP1 may be instrumental in sustaining the tumorigenic and metastatic phenotype and could represent a potential vulnerability in ERG fusion-positive tumors.
Objective: To test the activity of EC-8042, a compound able to block SP1, in cellular and mouse models of ERG-positive prostate cancer.
Prostate cancer is the most common malignancy in men and the second cause of cancer-related deaths in western countries. Despite the progress in the treatment of localized prostate cancer, there is still lack of effective therapies for the advanced forms of the disease. Most patients with advanced prostate cancer become resistant to androgen deprivation therapy (ADT), which remains the main therapeutic option in this setting, and progress to lethal metastatic castration-resistant prostate cancer (mCRPC).
View Article and Find Full Text PDFCancer stem cells (CSCs) contribute to disease progression and treatment failure in human cancers. The balance among self-renewal, differentiation, and senescence determines the expansion or progressive exhaustion of CSCs. Targeting these processes might lead to novel anticancer therapies.
View Article and Find Full Text PDFThe main aim of this study was to investigate the putative association among the presence of prostate cancer cells, defined as prostate osteoblast-like cells (POLCs), and showing the expression of typical morphological and molecular characteristics of osteoblasts, the development of bone metastasis within 5 years of diagnosis, and the uptake of 18F-choline evaluated by PET/CT analysis. To this end, prostate biopsies ( = 110) were collected comprising 44 benign lesions and 66 malignant lesions. Malignant lesions were further subdivided into two groups: biopsies from patients that had clinical evidence of bone metastasis (BM+, = 23) and biopsies from patients that did not have clinical evidence of bone metastasis within 5 years (BM-, = 43).
View Article and Find Full Text PDFMotivation: Long non-coding RNAs (lncRNAs) have gained increasing relevance in epigenetic regulation and nuclear functional organization. High-throughput sequencing approaches have revealed frequent non-coding transcription in promoter-proximal regions. However, a comprehensive catalogue of promoter-associated RNAs (paRNAs) and an analysis of the possible interactions with neighboring genes and genomic regulatory elements are missing.
View Article and Find Full Text PDFProstate cancer (PCa) is the most common malignant visceral neoplasm in males in Western countries. Despite progress made in the early treatment of localized malignancies, there remains a need for therapies effective against advanced forms of the disease. Genetically engineered mouse (GEM) models are valuable tools for addressing this issue, particularly in defining the cellular and molecular mechanisms responsible for tumor initiation and progression.
View Article and Find Full Text PDFLong noncoding RNAs are emerging players in the epigenetic machinery with key roles in development and diseases. Here we uncover a complex network comprising a promoter-associated noncoding RNA (paRNA), microRNA and epigenetic regulators that controls transcription of the tumour suppressor E-cadherin in epithelial cancers. E-cadherin silencing relies on the formation of a complex between the paRNA and microRNA-guided Argonaute 1 that, together, recruit SUV39H1 and induce repressive chromatin modifications in the gene promoter.
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