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10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug...
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10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 28254

Special Issue Editor

Prof. Dr. Shu-Pin Huang

E-Mail Website
Guest Editor
Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Interests: prostate cancer; uro-oncology; biomarkers; targeted therapy; precision medicine; molecular epidemiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The year 2023 marks the 10th anniversary of Biomedicines, a peer-reviewed open access journal in the biomedical field. So far, Biomedicines has published more than 2700 papers from more than 17,000 authors. We appreciate each author, reviewer, and academic editor whose support has brought us to where we are today.

To celebrate this significant milestone, we aim to publish a Special Issue entitled “10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug resistance, Biomarkers, and beyond”. Prostate cancer is the second most common cancer affecting men worldwide, with 1.4 million new cases in 2020. The etiology of prostate cancer remains largely unknown; in addition to aging and ethnicity, genetic and environmental factors are believed to contribute to the development of prostate cancer. Prostate cancer is characterized as molecularly heterogeneous, and its natural history is highly variable, which leads to different treatment modality from active surveillance to aggressive treatment. Understanding these biological alterations behind is crucial in determining the course of the disease and providing a guide for therapy. Although most prostate cancers initially respond to androgen deprivation therapy (ADT), they gradually develop resistance and progress to castration-resistant prostate cancer (CRPC), which eventually becomes lethal. Understanding the mechanisms of CRPC will help us to develop novel treatment strategies and predict drug response toward precision medicine. We welcome multidisciplinary research articles that will enhance our knowledge on prostate cancer.

Prof. Dr. Shu-Pin Huang
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prostate cancer
  • biology and genetic study
  • biomarkers
  • novel treatment strategy
  • drug resistance mechanism
  • castration resistant prostate cancer (CRPC)
  • tumor microenvironment
  • cancer stem cell
  • precision medicine
  • prediction model

Related Special Issue

Published Papers (16 papers)

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Research

Jump to: Review

12 pages, 1975 KiB  
Article
Pretest PSA and Restaging PSMA PET/CT Predict Survival in Biochemically Recurrent Prostate Cancer
by Rie von Eyben, Manuela Andrea Hoffmann, Cigdem Soydal, Irene Virgolini, Murat Tuncel, Mathieu Gauthé, Daniel S. Kapp and Finn Edler von Eyben
Biomedicines 2023, 11(9), 2333; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11092333 - 22 Aug 2023
Cited by 1 | Viewed by 891
Abstract
Background: A biochemical recurrence (BCR) risk model was created based on pretest prostate specific antigen (PSA) and groupings by restaging prostate specific membrane antigen (PSMA) PET/CT. Methods: A cohort of 1216 BCR patients were analyzed for overall survival (OS) according to the PSA [...] Read more.
Background: A biochemical recurrence (BCR) risk model was created based on pretest prostate specific antigen (PSA) and groupings by restaging prostate specific membrane antigen (PSMA) PET/CT. Methods: A cohort of 1216 BCR patients were analyzed for overall survival (OS) according to the PSA threshold and restaging PSMA PET/CT. A Cox regression analysis of OS was carried out to detect significant clinical characteristics. Results: In the cohort, 271 patients had a pretest PSA of <0.5 ng/mL and 945 patients had higher PSA values. The restaging PSMA PET/CT was positive for 834 patients and negative for 369. Of 1203 patients, 133 (11%) died, including 19 of the 369 (5%) patients without positive sites on the restaging PSMA PET/CT, 82 of the 711 (12%) with 1–5 positive sites, and 32 of the 123 (26%) with >5 positive sites. In the Cox regression analysis, four variables significantly predicted OS: treatment center, International Society of Urologic Pathology (ISUP) grade, pretest PSA threshold, and the grouping of positive sites on the restaging PSMA PET/CT. Conclusions: The pretest PSA and PSMA PET/CT were important for the OS of the BCR patients. The findings argue for the new BCR risk model and serve as framework for ongoing trials. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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15 pages, 2257 KiB  
Article
Enhancing the Anticancer and Anti-Inflammatory Properties of Curcumin in Combination with Quercetin, for the Prevention and Treatment of Prostate Cancer
by Michele Pellegrino, Emilia Bevacqua, Luca Frattaruolo, Anna Rita Cappello, Stefano Aquaro and Paola Tucci
Biomedicines 2023, 11(7), 2023; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11072023 - 18 Jul 2023
Viewed by 1615
Abstract
Prostate cancer is the second most common cancer in men. Although epidemiologic studies show that a higher intake of polyphenols, curcumin (CUR), and quercetin (QRT), in particular, result in lower prostate cancer risk, the chemopreventive mechanisms underlying the effects of CUR and QRT [...] Read more.
Prostate cancer is the second most common cancer in men. Although epidemiologic studies show that a higher intake of polyphenols, curcumin (CUR), and quercetin (QRT), in particular, result in lower prostate cancer risk, the chemopreventive mechanisms underlying the effects of CUR and QRT have not been fully understood yet, and most investigations were conducted with individual compounds. Here, we investigated the anticancer and anti-inflammatory effects of CUR in combination with QRT, respectively, in a human prostate cancer cell line, PC-3, and in LPS-stimulated RAW 264.7 cells, and found that their combination significantly inhibited proliferation and arrested the cell cycle, inducing apoptosis, so exhibiting synergic activities stronger than single drug use. Moreover, via their antioxidant effects, the combination of CUR and QRT modulated several inflammation-mediated signaling pathways (ROS, nitric oxide, and pro-inflammatory cytokines) thus helping protect cells from undergoing molecular changes that trigger carcinogenesis. Although additional studies, including in vivo experiments and translational studies, are required, this study raises the possibility of their use as a safe, effective, and affordable therapeutic approach to prostate cancer. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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10 pages, 908 KiB  
Article
Comparison of Prostate-Specific Antigen and Its Density and Prostate Health Index and Its Density for Detection of Prostate Cancer
by Youngjun Boo, Jae Hoon Chung, Minyong Kang, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee and Wan Song
Biomedicines 2023, 11(7), 1912; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11071912 - 06 Jul 2023
Viewed by 986
Abstract
As the incidence of prostate cancer (PCa) has increased, screening based on prostate-specific antigen (PSA) has become controversial due to the low specificity of PSA. Therefore, we investigated the diagnostic performance of prostate health index (PHI) density (PHID) for the detection of PCa [...] Read more.
As the incidence of prostate cancer (PCa) has increased, screening based on prostate-specific antigen (PSA) has become controversial due to the low specificity of PSA. Therefore, we investigated the diagnostic performance of prostate health index (PHI) density (PHID) for the detection of PCa and clinically significant PCa (csPCa) compared to PSA, PSA density (PSAD), and PHI as a triaging test. We retrospectively reviewed 306 men who underwent prostate biopsy for PSA levels of 2.5 to 10 ng/mL between January 2020 and April 2023. Of all cohorts, 86 (28.1%) and 48 (15.7%) men were diagnosed with PCa and csPCa, respectively. In ROC analysis, the highest AUC was identified for PHID (0.812), followed by PHI (0.791), PSAD (0.650), and PSA (0.571) for PCa. A similar trend was observed for csPCa: PHID (AUC 0.826), PHI (AUC 0.796), PSAD (AUC 0.671), and PSA (0.552). When the biopsy was restricted to men with a PHID ≥ 0.56, 26.5% of unnecessary biopsies could be avoided; however, 9.3% of PCa cases and one csPCa case (2.1%) remained undiagnosed. At approximately 90% sensitivity for csPCa, at the given cut-off values of PHI ≥ 36.4, and PHID ≥ 0.91, 48.7% and 49.3% of unnecessary biopsies could be avoided. In conclusion, PHID had a small advantage over PHI, about 3.6%, for the reduction in unnecessary biopsies for PCa. The PHID and PHI showed almost the same diagnostic performance for csPCa detection. PHID can be used as a triaging test in a clinical setting to pre-select the risk of PCa and csPCa. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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12 pages, 988 KiB  
Article
Association of TP53 Single Nucleotide Polymorphisms with Prostate Cancer in a Racially Diverse Cohort of Men
by Allison Duncan, Darryl Nousome, Randy Ricks, Huai-Ching Kuo, Lakshmi Ravindranath, Albert Dobi, Jennifer Cullen, Shiv Srivastava, Gregory T. Chesnut, Gyorgy Petrovics and Indu Kohaar
Biomedicines 2023, 11(5), 1404; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11051404 - 09 May 2023
Viewed by 1453
Abstract
Growing evidence indicates the involvement of a genetic component in prostate cancer (CaP) susceptibility and clinical severity. Studies have reported the role of germline mutations and single nucleotide polymorphisms (SNPs) of TP53 as possible risk factors for cancer development. In this single institutional [...] Read more.
Growing evidence indicates the involvement of a genetic component in prostate cancer (CaP) susceptibility and clinical severity. Studies have reported the role of germline mutations and single nucleotide polymorphisms (SNPs) of TP53 as possible risk factors for cancer development. In this single institutional retrospective study, we identified common SNPs in the TP53 gene in AA and CA men and performed association analyses for functional TP53 SNPs with the clinico-pathological features of CaP. The SNP genotyping analysis of the final cohort of 308 men (212 AA; 95 CA) identified 74 SNPs in the TP53 region, with a minor allele frequency (MAF) of at least 1%. Two SNPs were non-synonymous in the exonic region of TP53: rs1800371 (Pro47Ser) and rs1042522 (Arg72Pro). The Pro47Ser variant had an MAF of 0.01 in AA but was not detected in CA. Arg72Pro was the most common SNP, with an MAF of 0.50 (0.41 in AA; 0.68 in CA). Arg72Pro was associated with a shorter time to biochemical recurrence (BCR) (p = 0.046; HR = 1.52). The study demonstrated ancestral differences in the allele frequencies of the TP53 Arg72Pro and Pro47Ser SNPs, providing a valuable framework for evaluating CaP disparities among AA and CA men. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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12 pages, 865 KiB  
Article
Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients
by Tomas Januskevicius, Rasa Sabaliauskaite, Daiva Dabkeviciene, Ieva Vaicekauskaite, Ilona Kulikiene, Agne Sestokaite, Asta Vidrinskaite, Arnas Bakavicius, Feliksas Jankevicius, Albertas Ulys and Sonata Jarmalaite
Biomedicines 2023, 11(3), 761; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11030761 - 02 Mar 2023
Cited by 2 | Viewed by 1557
Abstract
(1) Background: DNA damage response (DDR) pathway gene mutations are detectable in a significant number of patients with metastatic castration-resistant prostate cancer (mCRPC). The study aimed at identification of germline and/or somatic DDR mutations in blood and urine samples from patients with mCRPC [...] Read more.
(1) Background: DNA damage response (DDR) pathway gene mutations are detectable in a significant number of patients with metastatic castration-resistant prostate cancer (mCRPC). The study aimed at identification of germline and/or somatic DDR mutations in blood and urine samples from patients with mCRPC for correlation with responses to entire sequence of systemic treatment and survival outcomes. (2) Methods: DDR gene mutations were assessed prospectively in DNA samples from leukocytes and urine sediments from 149 mCRPC patients using five-gene panel targeted sequencing. The impact of DDR status on progression-free survival, as well as treatment-specific and overall survival, was evaluated using Kaplan–Meier curves and Cox regression. (3) Results: DDR mutations were detected in 16.6% of urine and 15.4% of blood samples. BRCA1, BRCA2, CHEK2, ATM and NBN mutations were associated with significantly shorter PFS in response to conventional androgen deprivation therapy and first-line mCRPC therapy with abiraterone acetate. Additionally, BRCA1 and BRCA2 mutation-bearing patients had a significantly worse response to radium-223. However, DDR mutation status was predictive for the favourable effect of second-line abiraterone acetate after previous taxane-based chemotherapy. (4) Conclusions: Our data confirm the benefit of non-invasive urine-based genetic testing for timely identification of high-risk prostate cancer cases for treatment personalization. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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9 pages, 3394 KiB  
Article
Racial Differences in Androgen Receptor (AR) and AR Splice Variants (AR-SVs) Expression in Treatment-Naïve Androgen-Dependent Prostate Cancer
by Farhan Khan, Obianuju Mercy Anelo, Qandeel Sadiq, Wendy Effah, Gary Price, Daniel L. Johnson, Suriyan Ponnusamy, Brandy Grimes, Michelle L. Morrison, Jay H. Fowke, D. Neil Hayes and Ramesh Narayanan
Biomedicines 2023, 11(3), 648; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11030648 - 21 Feb 2023
Cited by 1 | Viewed by 1396
Abstract
Androgen receptor splice variants (AR-SVs) contribute to the aggressive growth of castration-resistant prostate cancer (CRPC). AR-SVs, including AR-V7, are expressed in ~30% of CRPC, but minimally in treatment-naïve primary prostate cancer (PCa). Compared to Caucasian American (CA) men, African American (AA) men are [...] Read more.
Androgen receptor splice variants (AR-SVs) contribute to the aggressive growth of castration-resistant prostate cancer (CRPC). AR-SVs, including AR-V7, are expressed in ~30% of CRPC, but minimally in treatment-naïve primary prostate cancer (PCa). Compared to Caucasian American (CA) men, African American (AA) men are more likely to be diagnosed with aggressive/potentially lethal PCa and have shorter disease-free survival. Expression of a truncated AR in an aggressively growing patient-derived xenograft developed with a primary PCa specimen from an AA patient led us to hypothesize that the expression of AR-SVs could be an indicator of aggressive growth both in PCa progression and at the CRPC stage in AA men. Tissue microarrays (TMAs) were created from formalin-fixed paraffin-embedded (FFPE) prostatectomy tumor blocks from 118 AA and 115 CA treatment-naïve PCa patients. TMAs were stained with AR-V7-speicifc antibody and with antibodies binding to the N-terminus domain (NTD) and ligand-binding domain (LBD) of the AR. Since over 20 AR-SVs have been identified, and most AR-SVs do not as yet have a specific antibody, we considered a 2.0-fold or greater difference in the NTD vs. LBD staining as indication of potential AR-SV expression. Two AA, but no CA, patient tumors stained positively for AR-V7. AR staining with NTD and LBD antibodies was robust in most patients, with 21% of patients staining at least 2-fold more for NTD than LBD, indicating that AR-SVs other than AR-V7 are expressed in primary treatment-naïve PCa. About 24% of the patients were AR-negative, and race differences in AR expression were not statistically significant. These results indicate that AR-SVs are not restricted to CRPC, but also are expressed in primary PCa at higher rate than previously reported. Future investigation of the relative expression of NTD vs. LBD AR-SVs could guide the use of newly developed treatments targeting the NTD earlier in the treatment paradigm. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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18 pages, 7421 KiB  
Article
Androgen-Independent Prostate Cancer Is Sensitive to CDC42-PAK7 Kinase Inhibition
by Hyunho Han, Cheol Keun Park, Young-Deuk Choi, Nam Hoon Cho, Jongsoo Lee and Kang Su Cho
Biomedicines 2023, 11(1), 101; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11010101 - 30 Dec 2022
Cited by 4 | Viewed by 1706
Abstract
Prostate cancer is a common form of cancer in men, and androgen-deprivation therapy (ADT) is often used as a first-line treatment. However, some patients develop resistance to ADT, and their disease is called castration-resistant prostate cancer (CRPC). Identifying potential therapeutic targets for this [...] Read more.
Prostate cancer is a common form of cancer in men, and androgen-deprivation therapy (ADT) is often used as a first-line treatment. However, some patients develop resistance to ADT, and their disease is called castration-resistant prostate cancer (CRPC). Identifying potential therapeutic targets for this aggressive subtype of prostate cancer is crucial. In this study, we show that statins can selectively inhibit the growth of these CRPC tumors that have lost their androgen receptor (AR) and have overexpressed the RNA-binding protein QKI. We found that the repression of microRNA-200 by QKI overexpression promotes the rise of AR-low mesenchymal-like CRPC cells. Using in silico drug/gene perturbation combined screening, we discovered that QKI-overexpressing cancer cells are selectively vulnerable to CDC42-PAK7 inhibition by statins. We also confirmed that PAK7 overexpression is present in prostate cancer that coexists with hyperlipidemia. Our results demonstrate a previously unseen mechanism of action for statins in these QKI-expressing AR-lost CRPCs. This may explain the clinical benefits of the drug and support the development of a biology-driven drug-repurposing clinical trial. This is an important finding that could help improve treatment options for patients with this aggressive form of prostate cancer. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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9 pages, 656 KiB  
Article
Cumulative Effect Assessment of Common Genetic Variants on Prostate Cancer: Preliminary Studies
by Anca Gabriela Pavel, Danae Stambouli, Gabriela Anton, Ismail Gener, Adrian Preda, Catalin Baston and Constantin Gingu
Biomedicines 2022, 10(11), 2733; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10112733 - 28 Oct 2022
Viewed by 1309
Abstract
Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people. Genome Wide Association studies (GWASs) have generated multiple genetic variants associated with prostate cancer (PC) risk. Taking into account previously identified genetic susceptibility variants, the purpose of our study [...] Read more.
Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people. Genome Wide Association studies (GWASs) have generated multiple genetic variants associated with prostate cancer (PC) risk. Taking into account previously identified genetic susceptibility variants, the purpose of our study was to determine the cumulative association between four common SNPs and the overall PC risk. A total of 78 specimens from both PC and benign prostate hyperplasia (BPH) patients were included in the study. Genotyping of all selected SNPs was performed using the TaqMan assay. The association between each SNP and the PC risk was assessed individually and collectively. Analysis of the association between individual SNPs and PC risk revealed that only the rs4054823 polymorphism was significantly associated with PC, and not with BPH (p < 0.001). Statistical analysis also showed that the heterozygous genotype of the rs2735839 polymorphism is more common within the BPH group than in the PC group (p = 0.042). The cumulative effect of high-risk alleles on PC was analyzed using a logistic regression model. As a result, the carriers of at least one risk allele copy in each particular region had a cumulative odd ratio (OR) of 1.42 times, compared to subjects who did not have any of these factors. In addition, the combination of these four genetic variants increased the overall risk of PC by 52%. Our study provides further evidence of the cumulative effects of genetic risk factors on overall PC risk. These results should encourage future research to explain the interactions between known susceptibility variants and their contribution to the development and progression of PC disease. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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11 pages, 1706 KiB  
Article
Serum CCL2 Is a Prognostic Biomarker for Non-Metastatic Castration-Sensitive Prostate Cancer
by Hiroaki Iwamoto, Kouji Izumi, Ryunosuke Nakagawa, Ren Toriumi, Shuhei Aoyama, Taiki Kamijima, Takafumi Shimada, Hiroshi Kano, Tomoyuki Makino, Renato Naito, Suguru Kadomoto, Hiroshi Yaegashi, Shohei Kawaguchi, Takahiro Nohara, Kazuyoshi Shigehara, Yoshifumi Kadono and Atsushi Mizokami
Biomedicines 2022, 10(10), 2369; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102369 - 22 Sep 2022
Cited by 3 | Viewed by 1326
Abstract
Purpose: Prostate-specific antigen (PSA) is a useful prostate cancer (PC) biomarker, but some cases reported that PSA does not correlate with the Gleason score. Serum chemokine (CC motif) ligand 2 (CCL2) has been reported to be a potential complementary PSA biomarker, but it [...] Read more.
Purpose: Prostate-specific antigen (PSA) is a useful prostate cancer (PC) biomarker, but some cases reported that PSA does not correlate with the Gleason score. Serum chemokine (CC motif) ligand 2 (CCL2) has been reported to be a potential complementary PSA biomarker, but it remains unclear whether it can be applied to non-metastatic castration-sensitive prostate cancer (nmCSPC) or each section of the stages. Serum CCL2′s usefulness was investigated as a prognostic nmCSPC biomarker in this study. Methods: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital from 2007 to 2013. A total of 230 patients with nmCSPC were included in this study of the 255 patients with histologically diagnosed prostate cancer. The serum CCL2 efficacy as a prognostic nmCSPC biomarker was investigated retrospectively. Results: An independent significant predictor of worse OS was CCL2 ≥ 280 pg/dL and CRP ≥ 0.5 mg/dL in multivariate analysis. Gleason score ≥ 8 and CCL2 ≥ 280 pg/dL were independent significant predictors of CRPC-free survival (CFS) worsening in multivariate analysis. Serum CCL2 was a predictive biomarker for OS and CFS in nmCSPC. Furthermore, CCL2 ≥ 280 pg/mL patients had significantly worse visceral metastasis-free survival than those with CCL2 < 280 pg/mL. Conclusion: This study is the first to demonstrate serum CCL2 utility as a biomarker to predict OS and CFS in nmCSPC. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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15 pages, 4033 KiB  
Article
Heat Shock Protein 27 Affects Myeloid Cell Activation and Interaction with Prostate Cancer Cells
by Debora Singer, Verena Ressel, Matthias B. Stope and Sander Bekeschus
Biomedicines 2022, 10(9), 2192; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092192 - 05 Sep 2022
Cited by 1 | Viewed by 1423
Abstract
Heat shock proteins are cytoprotective molecules induced by environmental stresses. The small heat shock protein 27 (Hsp27) is highly expressed under oxidative stress conditions, mediating anti-oxidative effects and blocking apoptosis. Since medical gas plasma treatment subjects cancer cells to a multitude of reactive [...] Read more.
Heat shock proteins are cytoprotective molecules induced by environmental stresses. The small heat shock protein 27 (Hsp27) is highly expressed under oxidative stress conditions, mediating anti-oxidative effects and blocking apoptosis. Since medical gas plasma treatment subjects cancer cells to a multitude of reactive oxygen species (ROS), inducing apoptosis and immunomodulation, probable effects of Hsp27 should be investigated. To this end, we quantified the extracellular Hsp27 in two prostate cancer cell lines (LNCaP, PC-3) after gas plasma-induced oxidative stress, showing a significantly enhanced release. To investigate immunomodulatory effects, two myeloid cell lines (THP-1 and HL-60) were also exposed to Hsp27. Only negligible effects on viability, intracellular oxidative milieu, and secretion profiles of the myeloid cells were found when cultured alone. Interestingly, prostate cancer-myeloid cell co-cultures showed altered secretion profiles with a significant decrease in vascular endothelial growth factor (VEGF) release. Furthermore, the myeloid surface marker profiles were changed, indicating an enhanced differentiation in co-culture upon Hsp27 treatment. Finally, we investigated morphological changes, proliferation, and interaction with prostate cancer cells, and found significant alterations in the myeloid cells, supporting the tendency to differentiate. Collectively, our results suggest an ambiguous effect of Hsp27 on myeloid cells in the presence of prostate cancer cells which needs to be further investigated. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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Review

Jump to: Research

19 pages, 2202 KiB  
Review
Uncovering the Secrets of Prostate Cancer’s Radiotherapy Resistance: Advances in Mechanism Research
by Feng Lyu, Shi-Yu Shang, Xian-Shu Gao, Ming-Wei Ma, Mu Xie, Xue-Ying Ren, Ming-Zhu Liu, Jia-Yan Chen, Shan-Shi Li and Lei Huang
Biomedicines 2023, 11(6), 1628; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11061628 - 03 Jun 2023
Cited by 2 | Viewed by 1965
Abstract
Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa’s pathogenesis. Our review aims to [...] Read more.
Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa’s pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial–mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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27 pages, 2101 KiB  
Review
Novel Histopathological Biomarkers in Prostate Cancer: Implications and Perspectives
by Paweł Kiełb, Kamil Kowalczyk, Adam Gurwin, Łukasz Nowak, Wojciech Krajewski, Roman Sosnowski, Tomasz Szydełko and Bartosz Małkiewicz
Biomedicines 2023, 11(6), 1552; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11061552 - 26 May 2023
Cited by 3 | Viewed by 2070
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa [...] Read more.
Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa is strictly related to the creation of a premetastatic niche, which can be detected by altered levels of specific biomarkers. To date, the risk factors for biochemical recurrence include lymph node status, prostate-specific antigen (PSA), PSA density (PSAD), body mass index (BMI), pathological Gleason score, seminal vesicle invasion, extraprostatic extension, and intraductal carcinoma. In the future, biomarkers might represent another prognostic factor, as discussed in many studies. In this review, we focus on histopathological biomarkers (particularly CD169 macrophages, neuropilin-1, cofilin-1, interleukin-17, signal transducer and activator of transcription protein 3 (STAT3), LIM domain kinase 1 (LIMK1), CD15, AMACR, prostate-specific membrane antigen (PSMA), Appl1, Sortilin, Syndecan-1, and p63) and their potential application in decision making regarding the prognosis and treatment of PCa patients. We refer to studies that found a correlation between the levels of biomarkers and tumor characteristics as well as clinical outcomes. We also hypothesize about the potential use of histopathological markers as a target for novel immunotherapeutic drugs or targeted radionuclide therapy, which may be used as adjuvant therapy in the future. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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14 pages, 3324 KiB  
Review
METCAM Is a Potential Biomarker for Predicting the Malignant Propensity of and as a Therapeutic Target for Prostate Cancer
by Jui-Chuang Wu and Guang-Jer Wu
Biomedicines 2023, 11(1), 205; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11010205 - 13 Jan 2023
Cited by 2 | Viewed by 1763
Abstract
Prostate cancer is the second leading cause of cancer-related death worldwide. This is because it is still unknown why indolent prostate cancer becomes an aggressive one, though many risk factors for this type of cancer have been suggested. Currently, many diagnostic markers have [...] Read more.
Prostate cancer is the second leading cause of cancer-related death worldwide. This is because it is still unknown why indolent prostate cancer becomes an aggressive one, though many risk factors for this type of cancer have been suggested. Currently, many diagnostic markers have been suggested for predicting malignant prostatic carcinoma cancer; however, only a few, such as PSA (prostate-specific antigen), Prostate Health Index (PHI), and PCA3, have been approved by the FDA. However, each biomarker has its merits as well as shortcomings. The serum PSA test is incapable of differentiating prostate cancer from BPH and also has an about 25% false-positive prediction rate for the malignant status of cancer. The PHI test has the potential to replace the PSA test for the discrimination of BPH from prostate cancer and for the prediction of high-grade cancer avoiding unnecessary biopsies; however, the free form of PSA is unstable and expensive. PCA3 is not associated with locally advanced disease and is limited in terms of its prediction of aggressive cancer. Currently, several urine biomarkers have shown high potential in terms of being used to replace circulating biomarkers, which require a more invasive method of sample collection, such as via serum. Currently, the combined multiple tumor biomarkers may turn out to be a major trend in the diagnosis and assessment of the treatment effectiveness of prostate cancer. Thus, there is still a need to search for more novel biomarkers to develop a perfect cocktail, which consists of multiple biomarkers, in order to predict malignant prostate cancer and follow the efficacy of the treatment. We have discovered that METCAM, a cell adhesion molecule in the Ig-like superfamily, has great potential regarding its use as a biomarker for differentiating prostate cancer from BPH, predicting the malignant propensity of prostate cancer at the early premalignant stage, and differentiating indolent prostate cancers from aggressive cancers. Since METCAM has also been shown to be able to initiate the spread of prostate cancer cell lines to multiple organs, we suggest that it may be used as a therapeutic target for the clinical treatment of patients with malignant prostate cancer. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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24 pages, 1841 KiB  
Review
Liquid Biopsy in Diagnosis and Prognosis of Non-Metastatic Prostate Cancer
by Alexey S. Rzhevskiy, Alina Y. Kapitannikova, Denis V. Butnaru, Evgeniy V. Shpot, Simon A. Joosse, Andrei V. Zvyagin and Majid Ebrahimi Warkiani
Biomedicines 2022, 10(12), 3115; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10123115 - 02 Dec 2022
Cited by 7 | Viewed by 1970
Abstract
Currently, sensitive and specific methods for the detection and prognosis of early stage PCa are lacking. To establish the diagnosis and further identify an appropriate treatment strategy, prostate specific antigen (PSA) blood test followed by tissue biopsy have to be performed. The combination [...] Read more.
Currently, sensitive and specific methods for the detection and prognosis of early stage PCa are lacking. To establish the diagnosis and further identify an appropriate treatment strategy, prostate specific antigen (PSA) blood test followed by tissue biopsy have to be performed. The combination of tests is justified by the lack of a highly sensitive, specific, and safe single test. Tissue biopsy is specific but invasive and may have severe side effects, and therefore is inappropriate for screening of the disease. At the same time, the PSA blood test, which is conventionally used for PCa screening, has low specificity and may be elevated in the case of noncancerous prostate tumors and inflammatory conditions, including benign prostatic hyperplasia and prostatitis. Thus, diverse techniques of liquid biopsy have been investigated to supplement or replace the existing tests of prostate cancer early diagnosis and prognostics. Here, we provide a review on the advances in diagnosis and prognostics of non-metastatic prostate cancer by means of various biomarkers extracted via liquid biopsy, including circulating tumor cells, exosomal miRNAs, and circulating DNAs. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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23 pages, 4854 KiB  
Review
The Performance of FDA-Approved PET Imaging Agents in the Detection of Prostate Cancer
by Mei Li, Roman Zelchan and Anna Orlova
Biomedicines 2022, 10(10), 2533; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102533 - 10 Oct 2022
Cited by 6 | Viewed by 2322
Abstract
Positron emission tomography (PET) incorporated with X-ray computed tomography (PET/CT) or magnetic resonance imaging (PET/MRI) is increasingly being used as a diagnostic tool for prostate cancer (PCa). In this review, we describe and evaluate the clinical performance of some Food and Drug Administration [...] Read more.
Positron emission tomography (PET) incorporated with X-ray computed tomography (PET/CT) or magnetic resonance imaging (PET/MRI) is increasingly being used as a diagnostic tool for prostate cancer (PCa). In this review, we describe and evaluate the clinical performance of some Food and Drug Administration (FDA)-approved agents used for visualizing PCa: [18F]FDG, [11C]choline, [18F]FACBC, [68Ga]Ga-PSMA-11, [18F]DCFPyL, and [18F]-NaF. We carried out a comprehensive literature search based on articles published from 1 January 2010 to 1 March 2022. We selected English language articles associated with the discovery, preclinical study, clinical study, and diagnostic performance of the imaging agents for the evaluation. Prostate-specific membrane antigen (PSMA)-targeted imaging agents demonstrated superior diagnostic performance in both primary and recurrent PCa, compared with [11C]choline and [18F]FACBC, both of which target dividing cells and are used especially in patients with low prostate-specific antigen (PSA) values. When compared to [18F]-NaF (which is suitable for the detection of bone metastases), PSMA-targeted agents were also capable of detecting lesions in the lymph nodes, soft tissues, and bone. However, a limitation of PSMA-targeted imaging was the heterogeneity of PSMA expression in PCa, and consequently, a combination of two PET tracers was proposed to overcome this obstacle. The preliminary studies indicated that the use of PSMA-targeted scanning is more cost efficient than conventional imaging modalities for high-risk PCa patients. Furthering the development of imaging agents that target PCa-associated receptors and molecules could improve PET-based diagnosis of PCa. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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21 pages, 981 KiB  
Review
Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease
by Bo-Ren Wang, Yu-An Chen, Wei-Hsiang Kao, Chih-Ho Lai, Ho Lin and Jer-Tsong Hsieh
Biomedicines 2022, 10(8), 1872; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10081872 - 03 Aug 2022
Cited by 8 | Viewed by 2872
Abstract
Prostate cancer (PCa) is a major diagnosed cancer among men globally, and about 20% of patients develop metastatic prostate cancer (mPCa) in the initial diagnosis. PCa is a typical androgen-dependent disease; thus, hormonal therapy is commonly used as a standard care for mPCa [...] Read more.
Prostate cancer (PCa) is a major diagnosed cancer among men globally, and about 20% of patients develop metastatic prostate cancer (mPCa) in the initial diagnosis. PCa is a typical androgen-dependent disease; thus, hormonal therapy is commonly used as a standard care for mPCa by inhibiting androgen receptor (AR) activities, or androgen metabolism. Inevitably, almost all PCa will acquire resistance and become castration-resistant PCa (CRPC) that is associated with AR gene mutations or amplification, the presence of AR variants, loss of AR expression toward neuroendocrine phenotype, or other hormonal receptors. Treating CRPC poses a great challenge to clinicians. Research efforts in the last decade have come up with several new anti-androgen agents to prolong overall survival of CRPC patients. In addition, many potential targeting agents have been at the stage of being able to translate many preclinical discoveries into clinical practices. At this juncture, it is important to highlight the emerging strategies including small-molecule inhibitors to AR variants, DNA repair enzymes, cell survival pathway, neuroendocrine differentiation pathway, radiotherapy, CRPC-specific theranostics and immune therapy that are underway or have recently been completed. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Advances in Prostate Cancer: Science Discovery, Drug Resistance, Biomarkers, and Beyond)
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