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Cutting Edge Advances in Prostate Cancer
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Cutting Edge Advances in Prostate Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (20 September 2024) | Viewed by 11572

Special Issue Editor

Dr. Holger Hans Herman Erb

E-Mail Website
Guest Editor
Department of Urology, Technical University Dresden, 01069 Dresden, Germany
Interests: prostate cancer; oncology; androgen receptor; stat-proteins; metabolism; tumor biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prostate cancer (PCa) is the second most common cancer in men. The latest statistics have shown that one in six men will be diagnosed with PCa during their lifetime. Risk factors for developing aggressive PCa include age, ethnicity, genetic predisposition, obesity, and dietary factors. PCa treatment depends on the tumor’s stage, the patient’s age and overall health, and tumor risk assessment. For non-metastasized PCa, radical prostatectomy or radiotherapy is the treatment of choice with curative intent. However, due to PCa’s high dependency on androgen receptor (AR) signaling, the gold standard for metastasized PCa treatment was dominated by androgen deprivation therapy (ADT) for a long time. However, recent advances have led to a change in the treatment landscape, and combination therapies and new treatment regimens are now approved to treat metastatic PCa. This Special Issue aims to discuss and reflect on all recent advances in basic, translational, and clinical prostate cancer research. Therefore, manuscripts investigating new therapeutic strategies, prognostic as well as diagnostic biomarkers, and resistant mechanisms to the new regimen are of special interest.

Dr. Holger Hans Herman Erb
Guest Editor

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Keywords

  • prostate cancer
  • prognostic and diagnostic biomarkers
  • therapy resistance
  • tumor microenvironment
  • molecular biology

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Published Papers (5 papers)

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Research

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24 pages, 11845 KiB  
Article
Apoptosis–Cell Cycle–Autophagy Molecular Mechanisms Network in Heterogeneous Aggressive Phenotype Prostate Hyperplasia Primary Cell Cultures Have a Prognostic Role
by Elena Matei, Manuela Enciu, Mihai Cătălin Roșu, Felix Voinea, Anca Florentina Mitroi, Mariana Deacu, Gabriela Isabela Băltățescu, Antonela-Anca Nicolau, Anca Chisoi, Mariana Aşchie and Anita Cristina Ionescu (Mitu)
Int. J. Mol. Sci. 2024, 25(17), 9329; https://doi.org/10.3390/ijms25179329 - 28 Aug 2024
Viewed by 1370
Abstract
Our study highlights the apoptosis, cell cycle, DNA ploidy, and autophagy molecular mechanisms network to identify prostate pathogenesis and its prognostic role. Caspase 3/7 expressions, cell cycle, adhesion glycoproteins, autophagy, nuclear shrinkage, and oxidative stress by flow-cytometry analysis are used to study the [...] Read more.
Our study highlights the apoptosis, cell cycle, DNA ploidy, and autophagy molecular mechanisms network to identify prostate pathogenesis and its prognostic role. Caspase 3/7 expressions, cell cycle, adhesion glycoproteins, autophagy, nuclear shrinkage, and oxidative stress by flow-cytometry analysis are used to study the BPH microenvironment’s heterogeneity. A high late apoptosis expression by caspases 3/7 activity represents an unfavorable prognostic biomarker, a dependent predictor factor for cell adhesion, growth inhibition by arrest in the G2/M phase, and oxidative stress processes network. The heterogeneous aggressive phenotype prostate adenoma primary cell cultures present a high S-phase category (>12%), with an increased risk of death or recurrence due to aneuploid status presence, representing an unfavorable prognostic biomarker, a dependent predictor factor for caspase 3/7 activity (late apoptosis and necrosis), and cell growth inhibition (G2/M arrest)-linked mechanisms. Increased integrin levels in heterogenous BPH cultures suggest epithelial–mesenchymal transition (EMT) that maintains an aggressive phenotype by escaping cell apoptosis, leading to the cell proliferation necessary in prostate cancer (PCa) development. As predictor biomarkers, the biological mechanisms network involved in apoptosis, the cell cycle, and autophagy help to establish patient prognostic survival or target cancer therapy development. Full article
(This article belongs to the Special Issue Cutting Edge Advances in Prostate Cancer)
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19 pages, 5157 KiB  
Article
Different Prostatic Tissue Microbiomes between High- and Low-Grade Prostate Cancer Pathogenesis
by Jae Heon Kim, Hoonhee Seo, Sukyung Kim, Md Abdur Rahim, Sujin Jo, Indrajeet Barman, Hanieh Tajdozian, Faezeh Sarafraz, Ho-Yeon Song and Yun Seob Song
Int. J. Mol. Sci. 2024, 25(16), 8943; https://doi.org/10.3390/ijms25168943 - 16 Aug 2024
Cited by 1 | Viewed by 1265
Abstract
Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and [...] Read more.
Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and low-grade prostate tumor (LGT) were compared utilizing next-generation sequencing (NGS) technology. The results showed abnormalities in the bacterial profiles between the HGT and LGT specimens, indicating alterations in the make-up of bacterial populations and gene functionalities. The HGT specimens showed higher frequencies of Cutibacterium, Pelomonas, and Corynebacterium genera than the LGT specimens. Cell proliferation and cytokine assays also showed a significant proliferation of prostate cancer cells and elevated cytokine levels in the cells treated with Cutibacterium, respectively, supporting earlier findings. In summary, the HGT and LGT specimens showed differences in bacterial populations, suggesting that different bacterial populations might characterize high-grade and low-grade prostate malignancies. Full article
(This article belongs to the Special Issue Cutting Edge Advances in Prostate Cancer)
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11 pages, 876 KiB  
Article
Direct Patlak Reconstruction of [68Ga]Ga-PSMA PET for the Evaluation of Primary Prostate Cancer Prior Total Prostatectomy: Results of a Pilot Study
by Sazan Rasul, Barbara Katharina Geist, Holger Einspieler, Harun Fajkovic, Shahrokh F. Shariat, Stefan Schmitl, Markus Mitterhauser, Rainer Bartosch, Werner Langsteger, Pascal Andreas Thomas Baltzer, Thomas Beyer, Daria Ferrara, Alexander R. Haug, Marcus Hacker and Ivo Rausch
Int. J. Mol. Sci. 2023, 24(18), 13677; https://doi.org/10.3390/ijms241813677 - 5 Sep 2023
Viewed by 1537
Abstract
To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 [...] Read more.
To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3–130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa. Full article
(This article belongs to the Special Issue Cutting Edge Advances in Prostate Cancer)
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Review

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23 pages, 1284 KiB  
Review
Organoids: An Emerging Precision Medicine Model for Prostate Cancer Research
by Mohammad Waseem and Bi-Dar Wang
Int. J. Mol. Sci. 2024, 25(2), 1093; https://doi.org/10.3390/ijms25021093 - 16 Jan 2024
Cited by 7 | Viewed by 4020
Abstract
Prostate cancer (PCa) has been known as the most prevalent cancer disease and the second leading cause of cancer mortality in men almost all over the globe. There is an urgent need for establishment of PCa models that can recapitulate the progress of [...] Read more.
Prostate cancer (PCa) has been known as the most prevalent cancer disease and the second leading cause of cancer mortality in men almost all over the globe. There is an urgent need for establishment of PCa models that can recapitulate the progress of genomic landscapes and molecular alterations during development and progression of this disease. Notably, several organoid models have been developed for assessing the complex interaction between PCa and its surrounding microenvironment. In recent years, PCa organoids have been emerged as powerful in vitro 3D model systems that recapitulate the molecular features (such as genomic/epigenomic changes and tumor microenvironment) of PCa metastatic tumors. In addition, application of organoid technology in mechanistic studies (i.e., for understanding cellular/subcellular and molecular alterations) and translational medicine has been recognized as a promising approach for facilitating the development of potential biomarkers and novel therapeutic strategies. In this review, we summarize the application of PCa organoids in the high-throughput screening and establishment of relevant xenografts for developing novel therapeutics for metastatic, castration resistant, and neuroendocrine PCa. These organoid-based studies are expected to expand our knowledge from basic research to clinical applications for PCa diseases. Furthermore, we also highlight the optimization of PCa cultures and establishment of promising 3D organoid models for in vitro and in vivo investigations, ultimately facilitating mechanistic studies and development of novel clinical diagnosis/prognosis and therapies for PCa. Full article
(This article belongs to the Special Issue Cutting Edge Advances in Prostate Cancer)
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22 pages, 1414 KiB  
Review
Synthetic Lethality by Co-Inhibition of Androgen Receptor and Polyadenosine Diphosphate-Ribose in Metastatic Prostate Cancer
by Mariangela Calabrese, Isabella Saporita, Fabio Turco, Silke Gillessen, Elena Castro, Ursula Maria Vogl, Rosario Francesco Di Stefano, Federica Maria Carfì, Stefano Poletto, Giovanni Farinea, Marcello Tucci and Consuelo Buttigliero
Int. J. Mol. Sci. 2024, 25(1), 78; https://doi.org/10.3390/ijms25010078 - 20 Dec 2023
Cited by 4 | Viewed by 2326
Abstract
Androgen receptor pathway inhibitors (ARPI) and polyadenosine diphosphate-ribose inhibitors (PARPi) are part of the standard of care in patients with metastatic castration-resistant prostate cancer (mCRPC). There is biological evidence that the association of ARPI and PARPi could have a synergistic effect; therefore, several [...] Read more.
Androgen receptor pathway inhibitors (ARPI) and polyadenosine diphosphate-ribose inhibitors (PARPi) are part of the standard of care in patients with metastatic castration-resistant prostate cancer (mCRPC). There is biological evidence that the association of ARPI and PARPi could have a synergistic effect; therefore, several ongoing clinical trials are investigating the efficacy of this combination with preliminary results that are not perfectly concordant in identifying patients who can obtain the most benefit from this therapeutic option. The purpose of this review is to describe the PARPi mechanisms of action and to analyze the biological mechanisms behind the interplay between the androgen receptor and the PARPi system to better understand the rationale of the ARPI + PARPi combinations. Furthermore, we will summarize the preliminary results of the ongoing studies on these combinations, trying to understand in which patients to apply. Finally, we will discuss the clinical implications of this combination and its possible future perspectives. Full article
(This article belongs to the Special Issue Cutting Edge Advances in Prostate Cancer)
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