Prostate Cancer: 2nd Edition

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 35255

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Guest Editor
1. Department of Zootechnics, School of Sciences and Technology, University of Évora, Évora, Portugal
2. Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Vila Real, Portugal
Interests: veterinary medicine; experimental animal models; anti-inflammatory drugs; physical exercise; tumor angiogenesis; lymphangiogenesis
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Guest Editor
1. Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
2. Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
Interests: animal models; in vivo studies; natural compounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The prostate is the largest accessory gland of the male reproductive tract. Together with seminal vesicles and bulbourethral glands, the prostate is responsible for the production of an alkaline fluid that forms part of the seminal fluid. The prostate of men over 40 years of age is commonly affected by several pathologies, such as benign prostate hyperplasia and cancer.

Prostate cancer is one of the most frequent cancers among the male population worldwide. According to the World Health Organization (WHO), in the year 2020, prostate cancer affected approximately 1.41 million men and was responsible for the death of 375,304 of them. Prostate cancer development is associated with several risk factors including older age, black ethnicity, a family history of the disease, an increased body mass index, and obesity. The risk of prostate cancer development may be reduced through the consumption of a healthy diet full of fruits and vegetables, practice of physical exercise, and maintenance of a healthy weight.

Despite several approaches being available for prostate cancer treatment, the number of prostate cancer deaths is continuously increasing, which emphasizes the need to search for new methods for precocious diagnosis and more effective treatment. Animal models including rodents have greatly contributed to the study of biopathology and the prevention and treatment of prostate cancer.

This Special Issue entitled “Prostate Cancer II” aims to publish original research works and reviews concerning the diagnosis, treatment, and prognosis of prostate cancer, highlighting new advances in this field.

Dr. Ana Faustino
Dr. Paula A. Oliveira
Guest Editors

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Published Papers (15 papers)

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Research

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12 pages, 466 KiB  
Article
Role of Perilesional Sampling of Patients Undergoing Fusion Prostate Biopsies
by Riccardo Lombardo, Giorgia Tema, Antonio Nacchia, Elisa Mancini, Sara Franco, Filippo Zammitti, Antonio Franco, Hannes Cash, Carmen Gravina, Alessio Guidotti, Giacomo Gallo, Nicola Ghezzo, Antonio Cicione, Andrea Tubaro, Riccardo Autorino and Cosimo De Nunzio
Life 2023, 13(8), 1719; https://doi.org/10.3390/life13081719 - 10 Aug 2023
Cited by 8 | Viewed by 1091
Abstract
Recently, researchers have proposed perilesional sampling during prostate biopsies to avoid systematic biopsies of patients at risk of prostate cancer. The aim of our study is to evaluate the role of perilesional sampling to avoid systematic biopsies of patients undergoing fusion biopsies. A [...] Read more.
Recently, researchers have proposed perilesional sampling during prostate biopsies to avoid systematic biopsies of patients at risk of prostate cancer. The aim of our study is to evaluate the role of perilesional sampling to avoid systematic biopsies of patients undergoing fusion biopsies. A prospective cohort of patients undergoing transrectal MRI transrectal fusion biopsies were consecutively enrolled. All the patients underwent systematic biopsies (SB), targeted biopsies (TB) and perilesional biopsies within 10 mm from the lesion (PB). The detection rates of different strategies were determined. A total of 262 patients were enrolled. The median age of those enrolled was 70 years. The mean BMI was 27 kg/m2, and the mean and prostate volume was 52 mL. A PIRADS score ≥ 4 was recorded in 163/262 (40%) patients. Overall, the detection rates of cancer were 43.5% (114/262) and 35% (92/262) for csPCa. The use of the target + peri-target strategy resulted in a detection of 32.8% (86/262) of cancer cases and of 29% (76/262) of csPCa cases (Grade Group > 2). Using the target plus peri-target approach resulted in us missing 18/262 (7%) of the csPCa cases, avoiding the diagnosis of 8/262 (3%) of nsPCa cases. A biopsy strategy including lesional and perilesional sampling could avoid unnecessary prostate biopsies. However, the risk of missing significant cancers is present. Future studies should assess the cost–benefit relationship of different strategies. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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12 pages, 1634 KiB  
Article
Hypofractionated Post-Prostatectomy Radiotherapy in 16 Fractions: A Single-Institution Outcome
by Pavol Dubinsky, Vladimir Vojtek, Katarina Belanova, Natalia Janickova, Noemi Balazova and Zuzana Tomkova
Life 2023, 13(7), 1610; https://doi.org/10.3390/life13071610 - 23 Jul 2023
Cited by 1 | Viewed by 1524
Abstract
Background: The optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with intensity-modulated radiotherapy. The treatment schedule selection was motivated by limited technology resources and was [...] Read more.
Background: The optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with intensity-modulated radiotherapy. The treatment schedule selection was motivated by limited technology resources and was radiobiologically dose-escalated. Methods: One hundred consecutive M0 patients with post-prostatectomy radiotherapy were evaluated. Radiotherapy indication was adjuvant (ART) in 19%, early-salvage (eSRT) in 46% and salvage (SRT) in 35%. The dose prescription for prostate bed planning target volume was 52.8 Gy in 16 fractions of 3.3 Gy. The Common Terminology Criteria v. 4 for Adverse Events scale was used for toxicity grading. Results: The median follow-up was 61 months. Five-year biochemical recurrence-free survival (bRFS) was 78.6%, distant metastases-free survival (DMFS) was 95.7% and overall survival was 98.8%. Treatment indication (ART or eSRT vs. SRT) was the only significant factor for bRFS (HR 0.15, 95% CI 0.05–0.47, p = 0.001) and DMFS (HR 0.16, 95% CI 0.03–0.90; p = 0.038). Acute gastrointestinal (GI) toxicity grade 2 was recorded in 24%, grade 3 in 2%, acute genitourinary (GU) toxicity grade 2 in 10% of patients, and no grade 3. A cumulative rate of late GI toxicity grade ≥ 2 was observed in 9% and late GU toxicity grade ≥ 2 in 16% of patients. Conclusions: The observed results confirmed efficacy and showed a higher than anticipated rate of early GI, late GI, and GU toxicity of post-prostatectomy radiobiologically dose-escalated hypofractionated radiotherapy in 16 daily fractions. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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10 pages, 936 KiB  
Article
Predictors of Urinary Continence Recovery after Laparoscopic-Assisted Radical Prostatectomy: Is Surgical Urethral Length the Only Key Factor?
by Alberto Ragusa, Aldo Brassetti, Francesco Prata, Andrea Iannuzzi, Pasquale Callè, Francesco Tedesco, Loris Cacciatore, Francesco Esperto, Giuseppe Simone, Roberto Mario Scarpa and Rocco Papalia
Life 2023, 13(7), 1550; https://doi.org/10.3390/life13071550 - 13 Jul 2023
Cited by 6 | Viewed by 1376
Abstract
Several efforts in recent years have been made to predict urinary continence (UC) recovery after radical prostatectomy. The aim of our study was to investigate the impact of surgical urethral length preservation (SULP) on urinary continence after LARP (laparoscopic-assisted radical prostatectomy). We retrospectively [...] Read more.
Several efforts in recent years have been made to predict urinary continence (UC) recovery after radical prostatectomy. The aim of our study was to investigate the impact of surgical urethral length preservation (SULP) on urinary continence after LARP (laparoscopic-assisted radical prostatectomy). We retrospectively queried our datasets from May 2021 to May 2022. After the application of exclusion criteria, a total of 100 patients who underwent LARP for prostate cancer at our institution were enrolled. Through a sterile ruler inserted by a 12 mm trocar, the length of the membranous urethra spared during LARP was assessed intra-operatively. The baseline and peri- and postoperative data of patients were collected, and UC was defined as 0 or 1 on a safety pad. The median SULP was 20.5 mm (IQR, 14.5–25), and the median intraoperative EBL were 150 mL (IQR, 100–200). The Kaplan–Meier curve showed a significant difference at 20 mm, which was used as the cut-off value for SULP (log-rank test, p < 0.001). Multivariate Cox proportional hazards models showed that SULP and EBL < 250 mL were associated with UC recovery (all p < 0.02). Surgical urethral length preservation seemed to improve early UC recovery after LARP. Further multicentric studies are needed to confirm our findings. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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11 pages, 1058 KiB  
Article
Chronological Changes of Lower Urinary Tract Symptoms in Elderly Patients with Prostate Cancer after Low-Dose-Rate Prostate Brachytherapy
by Kunihiro Tsuchiya, Makoto Kawase, Keita Nakane, Masahiro Nakano, Koji Iinuma, Daiki Kato, Manabu Takai, Yuki Tobisawa, Takayuki Mori, Hirota Takano, Tomoyasu Kumano, Masayuki Matsuo, Takayasu Ito and Takuya Koie
Life 2023, 13(7), 1507; https://doi.org/10.3390/life13071507 - 4 Jul 2023
Cited by 2 | Viewed by 1229
Abstract
Background: To compare chronological changes in lower urinary tract symptoms (LUTS) after low-dose-rate prostate extended-release therapy (LDR-BT) using the overactive bladder symptom score (OABSS) in patients aged ≥ 75 years (elderly group) versus those aged < 75 years (control group). Materials and Methods: [...] Read more.
Background: To compare chronological changes in lower urinary tract symptoms (LUTS) after low-dose-rate prostate extended-release therapy (LDR-BT) using the overactive bladder symptom score (OABSS) in patients aged ≥ 75 years (elderly group) versus those aged < 75 years (control group). Materials and Methods: Patients with prostate cancer who underwent LDR-BT at Gifu University Hospital were included in this study. The International Prostate Symptom Score (IPSS), OABSS, and quality of life-based on urinary symptoms (IPSS-QOL) were evaluated before and after LDR-BT. We compared chronological changes in IPSS, OABSS, and IPSS-QOL in the elderly group with those in the control group and assessed the association between the resolution of OABSS and clinicopathological covariates. Results: A total of 484 patients were enrolled in this study. In the elderly group, the total IPSS, OABSS, and frequency scores increased at 1 month postoperatively, whereas the control group showed an increase at 3 months postoperatively. Multivariate analysis identified changes from baseline to the maximum OABSS and pre-treatment OABSS as significant predictors of delayed resolution of OABSS after LDR-BT. Conclusions: Changes in pre-treatment OABSS and pre- and post-LDR-BT OABSS values were independent predictors of delayed resolution of OABSS; however, no correlation was found with age. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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11 pages, 908 KiB  
Article
Efficacy and Safety of Neoadjuvant Luteinizing Hormone-Releasing Hormone Antagonist and Tegafur-Uracil Chemohormonal Therapy for High-Risk Prostate Cancer
by Fumiya Sugino, Keita Nakane, Makoto Kawase, Shota Ueda, Masayuki Tomioka, Yasumichi Takeuchi, Risa Tomioka-Inagawa, Toyohiro Yamada, Sanae Namiki, Naotaka Kumada, Shinichi Takeuchi, Kota Kawase, Daiki Kato, Manabu Takai, Koji Iinuma, Yuki Tobisawa and Takuya Koie
Life 2023, 13(5), 1072; https://doi.org/10.3390/life13051072 - 23 Apr 2023
Cited by 1 | Viewed by 1475
Abstract
Background: This retrospective single-center cohort study evaluated the efficacy and safety of a combination of neoadjuvant luteinizing hormone-releasing hormone (LHRH) antagonist and tegafur-uracil (UFT) therapy (NCHT) and investigated the medical records of patients with high-risk PCa who underwent robot-assisted radical prostatectomy (RARP). The [...] Read more.
Background: This retrospective single-center cohort study evaluated the efficacy and safety of a combination of neoadjuvant luteinizing hormone-releasing hormone (LHRH) antagonist and tegafur-uracil (UFT) therapy (NCHT) and investigated the medical records of patients with high-risk PCa who underwent robot-assisted radical prostatectomy (RARP). The therapy was followed by RARP for high-risk PCa. Materials and Methods: The enrolled patients were divided into two groups: low-intermediate-risk PCa patients who underwent RARP without neoadjuvant therapy (non-high-risk) and those who underwent NCHT followed by RARP (high-risk group). This study enrolled 227 patients (126: non-high-risk and 101: high-risk group). Patients in the high-risk-group had high-grade cancer compared to those in the non-high-risk-group. Results: At the median follow-up period of 12.0 months, there were no PCa deaths; two patients (0.9%) died of other causes. Twenty patients developed biochemical recurrence (BCR); the median time until BCR was 9.9 months after surgery. The 2-year biochemical recurrence-free survival rates were 94.2% and 91.1% in the non-high-risk and high-risk-group, respectively (p = 0.465). Grade ≥3 NCHT-related adverse events developed in nine patients (8.9%). Conclusions: This study indicates that combining neoadjuvant LHRH antagonists and UFT followed by RARP may improve oncological outcomes in patients with high-risk PCa. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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13 pages, 1486 KiB  
Article
Learning Curve of Transperineal MRI/US Fusion Prostate Biopsy: 4-Year Experience
by Po-Fan Hsieh, Po-I Li, Wei-Ching Lin, Han Chang, Chao-Hsiang Chang, Hsi-Chin Wu, Yi-Huei Chang, Yu-De Wang, Wen-Chin Huang and Chi-Ping Huang
Life 2023, 13(3), 638; https://doi.org/10.3390/life13030638 - 24 Feb 2023
Cited by 7 | Viewed by 2994
Abstract
This study aimed to evaluate the learning curve of transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion biopsy in a team composed of a single surgeon, a single radiologist, and a single pathologist. We prospectively enrolled 206 patients undergoing MRI/US fusion prostate biopsy and [...] Read more.
This study aimed to evaluate the learning curve of transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion biopsy in a team composed of a single surgeon, a single radiologist, and a single pathologist. We prospectively enrolled 206 patients undergoing MRI/US fusion prostate biopsy and divided them into four cohorts by the year of biopsy. We analyzed temporal changes in clinically significant prostate cancer (csPC) detection rate, percentage of positive cores on biopsy, and Gleason upgrading rate after radical prostatectomy. The csPC detection rate by MRI/US fusion targeted biopsy (TB) increased significantly (from 35.3% to 60.0%, p = 0.01). With increased experience, the csPC detection rates for small (1 cm) and anterior target lesions gradually increased (from 41.2% to 51.6%, p = 0.5; from 54.5% to 88.2%, p = 0.8, respectively). The percentage of positive cores on TB increased significantly (from 18.4% to 44.2%, p = 0.001). The Gleason upgrading rate gradually decreased (from 22.2% to 11.1%, p = 0.4). In conclusion, with accumulated experience and teamwork, the csPC detection rate by TB significantly increased. Multidisciplinary team meetings and a free-hand biopsy technique were the key factors for overcoming the learning curve. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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18 pages, 4288 KiB  
Article
IND-2, a Quinoline Derivative, Inhibits the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress, Apoptosis and Inhibiting Topoisomerase II
by Swapnaa Balaji, Rabin Neupane, Saloni Malla, Rahul Khupse, Haneen Amawi, Shikha Kumari, Diwakar Bastihalli Tukaramrao, Srestha Chattopadhyay, Charles R. Ashby, Jr., Sai H. S. Boddu, Chandrabose Karthikeyan, Piyush Trivedi, Dayanidhi Raman and Amit K. Tiwari
Life 2022, 12(11), 1879; https://doi.org/10.3390/life12111879 - 14 Nov 2022
Cited by 7 | Viewed by 2295
Abstract
In men, prostate cancer (PC) is the most frequently diagnosed cancer, causing an estimated 375,000 deaths globally. Currently, existing therapies for the treatment of PC, notably metastatic cases, have limited efficacy due to drug resistance and problematic adverse effects. Therefore, it is imperative [...] Read more.
In men, prostate cancer (PC) is the most frequently diagnosed cancer, causing an estimated 375,000 deaths globally. Currently, existing therapies for the treatment of PC, notably metastatic cases, have limited efficacy due to drug resistance and problematic adverse effects. Therefore, it is imperative to discover and develop novel drugs for treating PC that are efficacious and do not produce intolerable adverse or toxic effects. Condensed quinolines are naturally occurring anticancer compounds. In this study, we determined the in vitro efficacy of IND-2 (4-chloro-2-methylpyrimido[1″,2″:1,5]pyrazolo[3,4-b]quinolone) in the PC lines, PC-3 and DU-145. IND-2 significantly inhibited the proliferation of PC-3 and DU-145, with IC50 values of 3 µM and 3.5 µM, respectively. The incubation of PC-3 cells with 5 and 10 µM of IND-2 caused the loss of the mitochondrial membrane potential in PC-3 cells. Furthermore, IND-2, at 5 µM, increased the expression of cleaved caspase-3, cleaved caspase-7 and cleaved poly (ADP-ribose) polymerase (PARP). The incubation of PC-3 cells with 5 µM of IND-2 significantly decreased the expression of the apoptotic protein, B-cell lymphoma 2 (Bcl-2). Furthermore, 5 and 10 µM of IND-2 produced morphological changes in PC-3 cells characteristic of apoptosis. Interestingly, IND-2 (2.5, 5 and 10 µM) also induced mitotic catastrophe in PC-3 cells, characterized by the accumulation of multinuclei. The incubation of DU-145 cells with 1.25 and 5 μM of IND-2 significantly increased the levels of reactive oxygen species (ROS). Finally, IND-2, at 10 μM, inhibited the catalytic activity of topoisomerase IIα. Overall, our findings suggest that IND-2 could be a potential lead compound for the development of more efficacious compounds for the treatment of PC. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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13 pages, 3834 KiB  
Article
Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis
by Praveenkumar Basavaraj, Phakkhathorn Ruangsai, Po-Fan Hsieh, Wen-Ping Jiang, Da-Tian Bau, Guan-Jhong Huang and Wen-Chin Huang
Life 2022, 12(11), 1769; https://doi.org/10.3390/life12111769 - 2 Nov 2022
Cited by 5 | Viewed by 1854
Abstract
Prostate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. [...] Read more.
Prostate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. To seek new remedies for the lethal PCa diseases is currently an urgent need. In this study, we endeavored to investigate the therapeutic efficacy of alpinumisoflavone (AIF), a natural product, in PCa. LNCaP (androgen- sensitive) and C4-2 (CRPC) PCa cells were used. An MTT-based method, soft agar colony forming assay, biological progression approaches were applied to determine cell viability, migration, and invasion. A fatty acid quantification kit, a cholesterol detection kit and oil red O staining were conducted to analyze the intracellular levels of lipids and cholesterols. Apoptosis assays were also performed. AIF reduced cell viability, migration, and invasion in PCa cells. The expression of androgen receptor (AR), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was substantially inhibited by AIF treatment in PCa cells. Furthermore, by inhibiting FASN and HMGCR expression, AIF decreased the amounts of intracellular fatty acids, cholesterols, and lipid droplets in PCa cells. Significantly, through coordinated targeting FASN- and HMGCR-regulated biosynthesis and the AR axis, AIF activated the caspase-associated apoptosis in PCa cells. These results collectively demonstrated for the first time the potential of AIF as a novel and attractive remedy and provided an alternative opportunity to cure PCa malignancy. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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Review

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14 pages, 1111 KiB  
Review
PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer: Unraveling the Therapeutic Landscape
by Ashaar Al-Akhras, Chadi Hage Chehade, Arshit Narang and Umang Swami
Life 2024, 14(2), 198; https://doi.org/10.3390/life14020198 - 30 Jan 2024
Cited by 6 | Viewed by 3904
Abstract
The treatment landscape of metastatic prostate cancer (mPCa) is rapidly evolving with the recent approvals of poly-ADP ribose polymerase inhibitors (PARPis) as monotherapy or as part of combination therapy with androgen receptor pathway inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC). Already [...] Read more.
The treatment landscape of metastatic prostate cancer (mPCa) is rapidly evolving with the recent approvals of poly-ADP ribose polymerase inhibitors (PARPis) as monotherapy or as part of combination therapy with androgen receptor pathway inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC). Already part of the therapeutic armamentarium in different types of advanced cancers, these molecules have shaped a new era in mPCa by targeting genomic pathways altered in these patients, leading to promising responses. These agents act by inhibiting poly-ADP ribose polymerase (PARP) enzymes involved in repairing single-strand breaks in the DNA. Based on the PROfound and TRITON3 trials, olaparib and rucaparib were respectively approved as monotherapy in pretreated patients with mCRPC and alterations in prespecified genes. The combinations of olaparib with abiraterone (PROpel) and niraparib with abiraterone (MAGNITUDE) were approved as first-line options in patients with mCRPC and alterations in BRCA1/2, whereas the combination of talazoparib with enzalutamide (TALAPRO-2) was approved in the same setting in patients with alterations in any of the HRR genes, which are found in around a quarter of patients with advanced prostate cancer. Additional trials are already underway to assess these agents in an earlier hormone-sensitive setting. Future directions will include refining the treatment sequencing in patients with mCRPC in the clinic while taking into account the financial toxicity as well as the potential side effects encountered with these therapies and elucidating their mechanism of action in patients with non-altered HRR genes. Herein, we review the biological rationale behind using PARPis in mCRPC and the key aforementioned clinical trials that paved the way for these approvals. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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23 pages, 1713 KiB  
Review
Prostate Cancer Microvascular Routes: Exploration and Measurement Strategies
by Fabio Grizzi, Mohamed A. A. A. Hegazi, Matteo Zanoni, Paolo Vota, Giovanni Toia, Maria Chiara Clementi, Cinzia Mazzieri, Maurizio Chiriva-Internati and Gianluigi Taverna
Life 2023, 13(10), 2034; https://doi.org/10.3390/life13102034 - 9 Oct 2023
Cited by 2 | Viewed by 1773
Abstract
Angiogenesis is acknowledged as a pivotal feature in the pathology of human cancer. Despite the absence of universally accepted markers for gauging the comprehensive angiogenic activity in prostate cancer (PCa) that could steer the formulation of focused anti-angiogenic treatments, the scrutiny of diverse [...] Read more.
Angiogenesis is acknowledged as a pivotal feature in the pathology of human cancer. Despite the absence of universally accepted markers for gauging the comprehensive angiogenic activity in prostate cancer (PCa) that could steer the formulation of focused anti-angiogenic treatments, the scrutiny of diverse facets of tumoral blood vessel development may furnish significant understanding of angiogenic processes. Malignant neoplasms, encompassing PCa, deploy a myriad of strategies to secure an adequate blood supply. These modalities range from sprouting angiogenesis and vasculogenesis to intussusceptive angiogenesis, vascular co-option, the formation of mosaic vessels, vasculogenic mimicry, the conversion of cancer stem-like cells into tumor endothelial cells, and vascular pruning. Here we provide a thorough review of these angiogenic mechanisms as they relate to PCa, discuss their prospective relevance for predictive and prognostic evaluations, and outline the prevailing obstacles in quantitatively evaluating neovascularization via histopathological examinations. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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16 pages, 619 KiB  
Review
Unmasking the Hidden Danger: A Decade-Long Systematic Review of Case–Control Studies on Single Occupational Risks and Prostate Cancer
by Caterina Ledda, Massimo Bracci, Alba Spadafora, Giuseppe Motta, Giuseppe Smecca, Dolores Catelan and Venerando Rapisarda
Life 2023, 13(9), 1820; https://doi.org/10.3390/life13091820 - 28 Aug 2023
Cited by 1 | Viewed by 2007
Abstract
The present systematic review addresses the influence of occupational exposures on prostate cancer risk. Eleven studies were analyzed for a range of occupational exposures, including but not limited to firefighting, physical activity, night shift work, chemical exposure, and solar ultraviolet radiation. The results [...] Read more.
The present systematic review addresses the influence of occupational exposures on prostate cancer risk. Eleven studies were analyzed for a range of occupational exposures, including but not limited to firefighting, physical activity, night shift work, chemical exposure, and solar ultraviolet radiation. The results of the review reveal that firefighters exposed to harmful substances, individuals engaged in physically strenuous work, and workers with chronic night shift routines showed an increased likelihood of developing prostate cancer. Moreover, the review identified an increased risk associated with exposure to certain chemicals, including alkylphenolic compounds and benzene-related substances. The evidence underscores the importance of considering the cumulative effect of multiple risk factors in a comprehensive risk assessment. However, the conclusions indicate the necessity for further research to deepen these relationships and develop more effective strategies for the prevention of prostate cancer. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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14 pages, 1052 KiB  
Review
Could Biparametric MRI Replace Multiparametric MRI in the Management of Prostate Cancer?
by Roxana Iacob, Emil-Robert Stoicescu, Simona Cerbu, Diana-Luminiţa Manolescu, Răzvan Bardan and Alin Cumpănaş
Life 2023, 13(2), 465; https://doi.org/10.3390/life13020465 - 7 Feb 2023
Cited by 9 | Viewed by 3611
Abstract
Prostate cancer (PCa) is a worldwide epidemiological problem, since it is one of the most prevalent types of neoplasia among men, and the third-leading cause of cancer-related deaths, after lung and colorectal tumors. Unfortunately, the early stages of PCa have a wide range [...] Read more.
Prostate cancer (PCa) is a worldwide epidemiological problem, since it is one of the most prevalent types of neoplasia among men, and the third-leading cause of cancer-related deaths, after lung and colorectal tumors. Unfortunately, the early stages of PCa have a wide range of unspecific symptoms. For these reasons, early diagnosis and accurate evaluation of suspicious lesions are crucial. Multiparametric MRI (mpMRI) is currently the imaging modality of choice for diagnostic screening and local staging of PCa, but also has a leading role in guiding biopsies and in treatment biparametric MRI (bpMRI) could partially replace mpMRI due to its lack of adverse reactions caused by contrast agents, relatively lower costs, and shorter acquisition time. Further, 31 relevant articles regarding the advantages and disadvantages of the aforementioned imaging techniques were scanned. As a result, while bpMRI has comparable accuracy in detecting PCa, its roles in the other steps of PCa management are limited. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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11 pages, 1041 KiB  
Review
Impact of Immune Cells in the Tumor Microenvironment of Prostate Cancer Metastasis
by Justin K. Messex and Geou-Yarh Liou
Life 2023, 13(2), 333; https://doi.org/10.3390/life13020333 - 26 Jan 2023
Cited by 13 | Viewed by 3023
Abstract
Prostate cancer is the most prevalent type of cancer in senior American men. Currently, the five-year survival rate after the initial diagnosis of prostate cancer is close to 100%. However, it is also the second leading cause of cancer death in senior men [...] Read more.
Prostate cancer is the most prevalent type of cancer in senior American men. Currently, the five-year survival rate after the initial diagnosis of prostate cancer is close to 100%. However, it is also the second leading cause of cancer death in senior men due to the dissemination of prostate cancer cells outside of the prostate causing growth in other organs, known as metastatic prostate cancer. The tumor microenvironment (TME) plays a critical role in the development, progression and metastasis of prostate cancer. One of the major components of the TME contains various types of immune cells, often recruited by cancer cells to the cancer formation areas. The interactions among prostate cancer cells and the infiltrating immune cells affect the outcome of prostate cancer. Here, we summarize the mechanisms various infiltrating immune cells use to regulate prostate cancer metastasis and possibly lead to the development of treatment strategies. Furthermore, the information here may also give rise to preventative strategies that focus on targeting the TME of prostate cancer patients. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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18 pages, 1381 KiB  
Review
Preclinical and Clinical Research Models of Prostate Cancer: A Brief Overview
by Debasish Basak, Lisney Gregori, Fatema Johora and Subrata Deb
Life 2022, 12(10), 1607; https://doi.org/10.3390/life12101607 - 14 Oct 2022
Cited by 4 | Viewed by 2891
Abstract
The incidence and mortality from prostate cancer (PCa) are on the rise which poses a major public health concern worldwide. In this narrative review, we have summarized the characteristics of major in vitro and in vivo PCa models including their utility in developing [...] Read more.
The incidence and mortality from prostate cancer (PCa) are on the rise which poses a major public health concern worldwide. In this narrative review, we have summarized the characteristics of major in vitro and in vivo PCa models including their utility in developing treatment strategies. Androgens, particularly, testosterone and dihydrotestosterone (DHT) activate the androgen receptor (AR) signaling pathway that facilitates the development and progression of castration resistant PCa. Several enzymes namely, CYP17A1, HSD17B, and SRD5A are essential to furnishing DHT from dehydroepiandrosterone in the classical pathway while DHT is formed from androstanediol in the backdoor pathway. The advancement in delineating the molecular heterogeneity of PCa has been possible through the development of several in vitro and in vivo research models. Generally, tissue culture models are advantageous to understand PCa biology and investigate the efficacy and toxicity of novel agents; nevertheless, animal models are indispensable to studying the PCa etiology and treatment since they can simulate the tumor microenvironment that plays a central role in initiation and progression of the disease. Moreover, the availability of several genetically engineered mouse models has made it possible to study the metastasis process. However, the conventional models are not devoid of limitations. For example, the lack of heterogeneity in tissue culture models and the variation of metastatic characteristics in xenograft models are obviously challenging. Additionally, due to the racial and ethnic disparities in PCa pathophysiology, a new model that can represent PCa encompassing different ethnicities is urgently needed. New models should continue to evolve to address the genetic and molecular complexities as well as to further elucidate the finer details of the steroidogenic pathway associated with PCa. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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12 pages, 1270 KiB  
Systematic Review
DNA Damage Repair Defects and Targeted Radionuclide Therapies for Prostate Cancer: Does Mutation Really Matter? A Systematic Review
by Luca Filippi, Barbara Palumbo, Oreste Bagni, Viviana Frantellizzi, Giuseppe De Vincentis and Orazio Schillaci
Life 2023, 13(1), 55; https://doi.org/10.3390/life13010055 - 24 Dec 2022
Cited by 7 | Viewed by 1949
Abstract
The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate cancer (PCa) submitted to radionuclide therapies with [223Ra]RaCl2 (223Ra-therapy) or [...] Read more.
The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate cancer (PCa) submitted to radionuclide therapies with [223Ra]RaCl2 (223Ra-therapy) or prostate specific membrane antigen (PSMA) ligands. A systematic literature search according to PRISMA criteria was made by using two main databases. Only studies published up until to October 2022 in the English language with ≥10 enrolled patients were selected. Seven studies including 326 pts, of whom 201 (61.6%) harboring DDR defects, were selected. The majority of selected papers were retrospective and four out of seven (57.1%) had small sample size (<50 pts). Three out of seven (42.8%) studies reported a more favorable outcome (overall or progression free survival) after therapy with alpha emitters (223Ra-therapy or [225Ac]Ac-PSMA-617) in subjects with DDR defects with respect to those without mutations. In two studies employing alpha or beta emitters ([177Lu]/[225Ac]-PMSA), no significant benefit was registered in pts harboring DDR defects. In all but one paper, no significant difference in response rate was reported among pts with or without DDR mutations. Although preliminary and biased by the retrospective design, preliminary data suggest a trend towards a longer survival in PCa pts harboring DDR defects submitted to radionuclide targeted therapy with alpha emitters. Full article
(This article belongs to the Special Issue Prostate Cancer: 2nd Edition)
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