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International Journal of Molecular... Aug 2023The incidence of prostate cancer (PC) has risen annually. PC mortality is explained by the metastatic disease (mPC). There is an intermediate scenario in which patients... (Review)
Review
The incidence of prostate cancer (PC) has risen annually. PC mortality is explained by the metastatic disease (mPC). There is an intermediate scenario in which patients have non-mPC but have initiated a metastatic cascade through epithelial-mesenchymal transition. There is indeed a need for more and better tools to predict which patients will progress in the future to non-localized clinical disease or already have micrometastatic disease and, therefore, will clinically progress after primary treatment. Biomarkers for the prediction of mPC are still under development; there are few studies and not much evidence of their usefulness. This review is focused on tissue-based genomic biomarkers (TBGB) for the prediction of metastatic disease. We develop four main research questions that we attempt to answer according to the current evidence. Why is it important to predict metastatic disease? Which tests are available to predict metastatic disease? What impact should there be on clinical guidelines and clinical practice in predicting metastatic disease? What are the current prostate cancer treatments? The importance of predicting metastasis is fundamental given that, once metastasis is diagnosed, quality of life (QoL) and survival drop dramatically. There is still a need and space for more cost-effective TBGB tests that predict mPC disease.
Topics: Male; Female; Humans; Quality of Life; Prostatic Neoplasms; Biomarkers; Genital Neoplasms, Female; Neoplasm Metastasis
PubMed: 37569883
DOI: 10.3390/ijms241512508 -
British Journal of Cancer Oct 2023Resistance to androgen receptor signalling inhibitors (ARSIs) represents a major clinical challenge in prostate cancer. We previously demonstrated that the ARSI...
BACKGROUND
Resistance to androgen receptor signalling inhibitors (ARSIs) represents a major clinical challenge in prostate cancer. We previously demonstrated that the ARSI enzalutamide inhibits only a subset of all AR-regulated genes, and hypothesise that the unaffected gene networks represent potential targets for therapeutic intervention. This study identified the hyaluronan-mediated motility receptor (HMMR) as a survival factor in prostate cancer and investigated its potential as a co-target for overcoming resistance to ARSIs.
METHODS
RNA-seq, RT-qPCR and Western Blot were used to evaluate the regulation of HMMR by AR and ARSIs. HMMR inhibition was achieved via siRNA knockdown or pharmacological inhibition using 4-methylumbelliferone (4-MU) in prostate cancer cell lines, a mouse xenograft model and patient-derived explants (PDEs).
RESULTS
HMMR was an AR-regulated factor that was unaffected by ARSIs. Genetic (siRNA) or pharmacological (4-MU) inhibition of HMMR significantly suppressed growth and induced apoptosis in hormone-sensitive and enzalutamide-resistant models of prostate cancer. Mechanistically, 4-MU inhibited AR nuclear translocation, AR protein expression and subsequent downstream AR signalling. 4-MU enhanced the growth-suppressive effects of 3 different ARSIs in vitro and, in combination with enzalutamide, restricted proliferation of prostate cancer cells in vivo and in PDEs.
CONCLUSION
Co-targeting HMMR and AR represents an effective strategy for improving response to ARSIs.
Topics: Male; Humans; Mice; Animals; Receptors, Androgen; Cell Line, Tumor; Prostatic Neoplasms; Nitriles; RNA, Small Interfering; Prostatic Neoplasms, Castration-Resistant; Drug Resistance, Neoplasm; Cell Proliferation
PubMed: 37673961
DOI: 10.1038/s41416-023-02406-8 -
Biochimica Et Biophysica Acta.... Oct 2023Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. The six transmembrane epithelial antigen of the prostate 1 (STEAP1) protein is...
Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. The six transmembrane epithelial antigen of the prostate 1 (STEAP1) protein is overexpressed in several types of human tumors, particularly in PCa. Our research group has demonstrated that STEAP1 overexpression is associated with PCa progression and aggressiveness. Therefore, understanding the cellular and molecular mechanisms triggered by STEAP1 overexpression will provide important insights to delineate new strategies for PCa treatment. In the present work, a proteomic strategy was used to characterize the intracellular signaling pathways and the molecular targets downstream of STEAP1 in PCa cells. A label-free approach was applied using an Orbitrap LC-MS/MS system to characterize the proteome of STEAP1-knockdown PCa cells. More than 6700 proteins were identified, of which a total of 526 proteins were found differentially expressed in scramble siRNA versus STEAP1 siRNA (234 proteins up-regulated and 292 proteins down-regulated). Bioinformatics analysis allowed us to explore the mechanism through which STEAP1 exerts influence on PCa, revealing that endocytosis, RNA transport, apoptosis, aminoacyl-tRNA biosynthesis, and metabolic pathways are the main biological processes where STEAP1 is involved. By immunoblotting, it was confirmed that STEAP1 silencing induced the up-regulation of cathepsin B, intersectin-1, and syntaxin 4, and the down-regulation of HRas, PIK3C2A, and DIS3. These findings suggested that blocking STEAP1 might be a suitable strategy to activate apoptosis and endocytosis, and diminish cellular metabolism and intercellular communication, leading to inhibition of PCa progression.
Topics: Male; Humans; Prostate; Proteomics; Chromatography, Liquid; Tandem Mass Spectrometry; Prostatic Neoplasms; RNA, Small Interfering; Antigens, Neoplasm; Oxidoreductases
PubMed: 37315586
DOI: 10.1016/j.bbamcr.2023.119522 -
European Journal of Nuclear Medicine... Oct 2023For the implementation of suitable radiation safety measures in [Lu]Lu-PSMA-617 therapy, additional insight into excretion kinetics is important. This study evaluates...
INTRODUCTION
For the implementation of suitable radiation safety measures in [Lu]Lu-PSMA-617 therapy, additional insight into excretion kinetics is important. This study evaluates this kinetics in prostate cancer patients via direct urine measurements.
METHODS
Both the short-term (up to 24 h, n = 28 cycles) and long-term kinetics (up to 7 weeks, n = 35 samples) were evaluated by collection of urine samples. Samples were measured on a scintillation counter to determine excretion kinetics.
RESULTS
The mean excretion half-time during the first 20 h was 4.9 h. Kinetics was significantly different for patients with kidney function below or above eGFR 65 ml/min. Calculated skin equivalent dose in case of urinary contamination was between 50 and 145 mSv when it was caused between 0 and 8 h p.i.. Measurable amounts of Lu were found in urine samples up to 18 days p.i..
CONCLUSION
Excretion kinetics of [Lu]Lu-PSMA-617 is especially relevant during the first 24 h, when accurate radiation safety measures are important to prevent skin contamination. Measures for accurate waste management are relevant up to 18 days.
Topics: Male; Humans; Radiopharmaceuticals; Prostate-Specific Antigen; Prostatic Neoplasms; Dipeptides; Heterocyclic Compounds, 1-Ring; Prostatic Neoplasms, Castration-Resistant; Lutetium
PubMed: 37421427
DOI: 10.1007/s00259-023-06328-8 -
Photodiagnosis and Photodynamic Therapy Jun 2024The global health issue of prostate cancer (PCa) requires better diagnosis and treatment. Photoacoustic imaging (PAI) may change PCa management. This review examines... (Review)
Review
The global health issue of prostate cancer (PCa) requires better diagnosis and treatment. Photoacoustic imaging (PAI) may change PCa management. This review examines PAI's principles, diagnostic role, and therapeutic guidance. PAI uses optical light excitation and ultrasonic detection for high-resolution functional and molecular imaging. PAI uses endogenous and exogenous contrast agents to distinguish cancerous and benign prostate tissues with greater sensitivity and specificity than PSA testing and TRUS-guided biopsy. In addition to diagnosing, PAI can guide and monitor PCa therapy. Its real-time imaging allows precise biopsies and brachytherapy seed placement. Photoacoustic temperature imaging allows non-invasive monitoring of thermal therapies like cryotherapy, improving treatment precision and success. Transurethral illumination probes, innovative contrast agents, integration with other imaging modalities, and machine learning analysis are being developed to overcome depth and data complexity restrictions. PAI could become an essential tool for PCa diagnosis and therapeutic guidance as the field advances.
Topics: Humans; Photoacoustic Techniques; Male; Prostatic Neoplasms
PubMed: 38821240
DOI: 10.1016/j.pdpdt.2024.104225 -
Prostate Cancer and Prostatic Diseases Dec 2023
Topics: Male; Humans; Prostatic Neoplasms; Exercise
PubMed: 36732363
DOI: 10.1038/s41391-023-00650-w -
BMC Cancer Jul 2023To explore the value of a multiparametric magnetic resonance imaging (MRI)-based deep learning model for the preoperative prediction of Ki67 expression in prostate...
BACKGROUND
To explore the value of a multiparametric magnetic resonance imaging (MRI)-based deep learning model for the preoperative prediction of Ki67 expression in prostate cancer (PCa).
MATERIALS
The data of 229 patients with PCa from two centers were retrospectively analyzed and divided into training, internal validation, and external validation sets. Deep learning features were extracted and selected from each patient's prostate multiparametric MRI (diffusion-weighted imaging, T2-weighted imaging, and contrast-enhanced T1-weighted imaging sequences) data to establish a deep radiomic signature and construct models for the preoperative prediction of Ki67 expression. Independent predictive risk factors were identified and incorporated into a clinical model, and the clinical and deep learning models were combined to obtain a joint model. The predictive performance of multiple deep-learning models was then evaluated.
RESULTS
Seven prediction models were constructed: one clinical model, three deep learning models (the DLRS-Resnet, DLRS-Inception, and DLRS-Densenet models), and three joint models (the Nomogram-Resnet, Nomogram-Inception, and Nomogram-Densenet models). The areas under the curve (AUCs) of the clinical model in the testing, internal validation, and external validation sets were 0.794, 0.711, and 0.75, respectively. The AUCs of the deep models and joint models ranged from 0.939 to 0.993. The DeLong test revealed that the predictive performance of the deep learning models and the joint models was superior to that of the clinical model (p < 0.01). The predictive performance of the DLRS-Resnet model was inferior to that of the Nomogram-Resnet model (p < 0.01), whereas the predictive performance of the remaining deep learning models and joint models did not differ significantly.
CONCLUSION
The multiple easy-to-use deep learning-based models for predicting Ki67 expression in PCa developed in this study can help physicians obtain more detailed prognostic data before a patient undergoes surgery.
Topics: Male; Humans; Nomograms; Deep Learning; Ki-67 Antigen; Retrospective Studies; Magnetic Resonance Imaging; Prostatic Neoplasms
PubMed: 37422624
DOI: 10.1186/s12885-023-11130-8 -
Annals of Medicine Dec 2024This comprehensive review aims to explore the potential applications of Gastrin-releasing peptide receptor (GRPR) in the diagnosis and treatment of prostate cancer.... (Review)
Review
This comprehensive review aims to explore the potential applications of Gastrin-releasing peptide receptor (GRPR) in the diagnosis and treatment of prostate cancer. Additionally, the study investigates the role of GRPR in prognostic assessment for individuals afflicted with prostate cancer. The review encompasses a thorough examination of existing literature and research studies related to the upregulation of GRPR in various tumor types, with a specific focus on prostate. The review also evaluates the utility of GRPR as a molecular target in prostate cancer research, comparing its significance to the well-established Prostate-specific membrane antigen (PSMA). The integration of radionuclide-targeted therapy with GRPR antagonists is explored as an innovative therapeutic approach for individuals with prostate cancer. Research findings suggest that GRPR serves as a promising molecular target for visualizing low-grade prostate cancer. Furthermore, it is demonstrated to complement the detection of lesions that may be negative for PSMA. The integration of radionuclide-targeted therapy with GRPR antagonists presents a novel therapeutic paradigm, offering potential benefits for individuals undergoing treatment for prostate cancer. In conclusion, this review highlights the emerging role of GRPR in prostate cancer diagnosis and treatment. Moreover, the integration of radionuclide-targeted therapy with GRPR antagonists introduces an innovative therapeutic approach that holds promise for improving outcomes in individuals dealing with prostate cancer. The potential prognostic value of GRPR in assessing the disease's progression adds another dimension to its clinical significance in the realm of urology.
Topics: Male; Humans; Receptors, Bombesin; Prostatic Neoplasms; Biomarkers; Up-Regulation; Radioisotopes
PubMed: 38442298
DOI: 10.1080/07853890.2024.2320301 -
Prostate Cancer and Prostatic Diseases Jun 2024Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant... (Review)
Review
BACKGROUND
Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant metastasis and mortality in patients with prognostically unfavorable features. These patients are best managed with a tailored treatment strategy incorporating risk stratification using clinicopathological factors, next-generation imaging, and genomic testing.
OBJECTIVE
This narrative review examines the utility of risk stratification for the management of patients with BCR in the context of clinical trial data, referencing the latest recommendations by European and US medical societies.
METHODS
PubMed was searched for relevant studies published through May 21 2023 on treatment of patients with BCR after radical prostatectomy (RP) or external beam radiotherapy (EBRT).
RESULTS
European and US guidelines support the risk-stratified management of BCR. Post-RP, salvage EBRT (with or without androgen deprivation therapy [ADT]) is an accepted treatment option for patients with BCR. Post-EBRT, local salvage therapies (RP, cryotherapy, high-intensity focused ultrasound, stereotactic body radiotherapy, and low-dose-rate and high-dose-rate brachytherapy) have demonstrated comparable relapse-free survival rates but differing adverse event profiles, short and long term. Local salvage therapies should be used for local-only relapses while ADT should be considered for regional or distant relapses. In practice, patients often receive ADT, with varying guidance for intermittent ADT vs. continuous ADT, due to consideration of quality-of-life effects.
CONCLUSIONS
Despite a lack of consensus for BCR treatment among guideline associations and medical societies, risk stratification of patients is essential for personalized treatment approaches, as it allows for an informed selection of therapeutic strategies and estimation of adverse events. In lower-risk disease, observation is recommended while in higher-risk disease, after failed repeat local therapy, ADT and/or clinical trial enrollment may be appropriate. Results from ongoing clinical studies of patients with BCR should provide consensus for management.
Topics: Humans; Male; Prostatic Neoplasms; Neoplasm Recurrence, Local; Risk Assessment; Prostatectomy; Prostate-Specific Antigen; Salvage Therapy; Prognosis; Androgen Antagonists
PubMed: 37679602
DOI: 10.1038/s41391-023-00712-z -
Military Medical Research Apr 2024In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging... (Review)
Review
In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine.
Topics: Male; Humans; Animals; Mice; Single-Cell Gene Expression Analysis; Prostatic Neoplasms; Immunotherapy; Prostate; Cell Differentiation
PubMed: 38605399
DOI: 10.1186/s40779-024-00526-7