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Biomedicines
Special Issues
Biomarkers and Therapy Targets in Urologic Cancer
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Biomarkers and Therapy Targets in Urologic Cancer

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 October 2020) | Viewed by 10968

Special Issue Editor

Dr. Oliver Hahn

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Guest Editor
Department of Urology, University Medical Center Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany
Interests: prostate cancer (PCa); chromatin remodeling; histone modifications; castration resistance; CRPC; androgen receptor; androgen deprivation; alternative splicin; hormone receptors; Epigenetics

Special Issue Information

Dear Colleagues,

The incidence of urologic cancers has been continuously rising over the past few years, with prostate cancer having become the most prevalent cancer in men in the US today. However, treatment of urogenital malignancies is still very broad. Personalized therapy, as it is already largely practiced, e.g., in melanoma or GIST tumors, only plays a very small role in our field, mostly due to the lack of specific prognostic or predictive markers and targeted therapies. This issue of Biomedicines will therefore specifically address such new therapies and potential markers, possibly bringing GU tumor therapy to the next level.

Dr. Oliver Hahn
Guest Editor

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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
  • urothelial cancer
  • bladder cancer
  • renal cell carcinoma
  • testicular cancer
  • penile cancer
  • biomarkers
  • targeted therapy
  • personalized medicine
  • genome-driven medicine

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Published Papers (4 papers)

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Research

12 pages, 2000 KiB  
Article
Prognostic Value of 18F-Choline PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Radium-223
by Luca Filippi, Gian Paolo Spinelli, Agostino Chiaravalloti, Orazio Schillaci, Francesco Equitani and Oreste Bagni
Biomedicines 2020, 8(12), 555; https://doi.org/10.3390/biomedicines8120555 - 30 Nov 2020
Cited by 12 | Viewed by 1922
Abstract
We aimed to investigate the role of positron emission computed tomography (PET/CT) with 18F-choline for predicting the outcome of metastatic castration-resistant prostate cancer (mCRPC) submitted to treatment with Radium-223 (223Ra-therapy). Clinical records of 20 mCRPC patients submitted to PET/CT with [...] Read more.
We aimed to investigate the role of positron emission computed tomography (PET/CT) with 18F-choline for predicting the outcome of metastatic castration-resistant prostate cancer (mCRPC) submitted to treatment with Radium-223 (223Ra-therapy). Clinical records of 20 mCRPC patients submitted to PET/CT with 18F-choline before 223Ra-therapy were retrospectively evaluated. The following PET-derived parameters were calculated: number of lesions, maximum and mean standardized uptake values (SUVmax, SUVmean), lean body mass corrected SUV peak (SULpeak), metabolic tumor volume (MATV), and total lesion activity (TLA). After 223Ra-therapy, all patients underwent regular follow-up until death. The predictive power of clinical and PET-derived parameters on overall survival (OS) was assessed by Kaplan–Meier analysis and the Cox proportional hazard method. All the patients showed 18F-choline-avid lesions at baseline PET/CT. Among the enrolled subjects, eleven (55%) completed all the six scheduled cycles of 223Ra-therapy; seven (35%) were responders according to imaging and biochemical parameters. Mean OS was 12.7 ± 1.4 months: by Kaplan–Meier analysis, number of lesions, PSA level and TLA were significantly correlated with OS. In multivariate Cox analysis, TLA remained the only significant predictor of survival (p = 0.003; hazard ratio = 7.6, 95% confidence interval = 1.9–29.5 months). 18F-choline PET may be useful for patients’ stratification before 223Ra-therapy. In particular, high metabolically active tumor burden (i.e., TLA) was predictive of poor outcome. Full article
(This article belongs to the Special Issue Biomarkers and Therapy Targets in Urologic Cancer)
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11 pages, 1322 KiB  
Article
Detection Rate of 68Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy
by Joachim Brumberg, Melanie Beckl, Alexander Dierks, Andreas Schirbel, Markus Krebs, Andreas Buck, Hubert Kübler, Constantin Lapa and Anna Katharina Seitz
Biomedicines 2020, 8(11), 511; https://doi.org/10.3390/biomedicines8110511 - 18 Nov 2020
Cited by 9 | Viewed by 2412
Abstract
Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on [...] Read more.
Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of 68Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All 68Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7% vs. 72.6%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended. Full article
(This article belongs to the Special Issue Biomarkers and Therapy Targets in Urologic Cancer)
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Figure 1

13 pages, 1795 KiB  
Article
Increased Expressions of Matrix Metalloproteinases (MMPs) in Prostate Cancer Tissues of Men with Type 2 Diabetes
by Andras Franko, Lucia Berti, Jörg Hennenlotter, Steffen Rausch, Marcus O. Scharpf, Martin Hrabĕ de Angelis, Arnulf Stenzl, Andreas Peter, Andreas L. Birkenfeld, Stefan Z. Lutz, Hans-Ulrich Häring and Martin Heni
Biomedicines 2020, 8(11), 507; https://doi.org/10.3390/biomedicines8110507 - 16 Nov 2020
Cited by 7 | Viewed by 2860
Abstract
Type 2 diabetes (T2D) is associated with worse prognosis of prostate cancer (PCa). The molecular mechanisms behind this association are still not fully understood. The aim of this study was to identify key factors, which contribute to the more aggressive PCa phenotype in [...] Read more.
Type 2 diabetes (T2D) is associated with worse prognosis of prostate cancer (PCa). The molecular mechanisms behind this association are still not fully understood. The aim of this study was to identify key factors, which contribute to the more aggressive PCa phenotype in patients with concurrent T2D. Therefore, we investigated benign and PCa tissue of PCa patients with and without diabetes using real time qPCR. Compared to patients without diabetes, patients with T2D showed a decreased E-cadherin/N-cadherin (CDH1/CDH2) ratio in prostate tissue, indicating a switch of epithelial-mesenchymal transition (EMT), which is a pivotal process in carcinogenesis. In addition, the gene expression levels of matrix metalloproteinases (MMPs) and CC chemokine ligands (CCLs) were higher in prostate samples of T2D patients. Next, prostate adenocarcinoma PC3 cells were treated with increasing glucose concentrations to replicate hyperglycemia in vitro. In these cells, high glucose induced expressions of MMPs and CCLs, which showed significant positive associations with the proliferation marker proliferating cell nuclear antigen (PCNA). These results indicate that in prostate tissue of men with T2D, hyperglycemia may induce EMT, increase MMP and CCL gene expressions, which in turn activate invasion and inflammatory processes accelerating the progression of PCa. Full article
(This article belongs to the Special Issue Biomarkers and Therapy Targets in Urologic Cancer)
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19 pages, 7186 KiB  
Article
Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells
by Magdalena Niemira, Barbara Borowa-Mazgaj, Samuel B. Bader, Adrianna Moszyńska, Marcin Ratajewski, Kaja Karaś, Mirosław Kwaśniewski, Adam Krętowski, Zofia Mazerska, Ester M. Hammond and Anna Skwarska
Biomedicines 2020, 8(9), 292; https://doi.org/10.3390/biomedicines8090292 - 19 Aug 2020
Cited by 5 | Viewed by 3363
Abstract
The androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and metastasis. Thus, blocking AR activity and its downstream signaling constitutes a major strategy for PCa treatment. Here, we report on the potent anti-PCa activity of a small-molecule imidazoacridinone, C-1311. [...] Read more.
The androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and metastasis. Thus, blocking AR activity and its downstream signaling constitutes a major strategy for PCa treatment. Here, we report on the potent anti-PCa activity of a small-molecule imidazoacridinone, C-1311. In AR-positive PCa cells, C-1311 was found to inhibit the transcriptional activity of AR, uncovering a novel mechanism that may be relevant for its anticancer effect. Mechanistically, C-1311 decreased the AR binding to the prostate-specific antigen (PSA) promoter, reduced the PSA protein level, and, as shown by transcriptome sequencing, downregulated numerous AR target genes. Importantly, AR-negative PCa cells were also sensitive to C-1311, suggesting a promising efficacy in the androgen-independent PCa sub-type. Irrespective of AR status, C-1311 induced DNA damage, arrested cell cycle progression, and induced apoptosis. RNA sequencing indicated significant differences in the transcriptional response to C-1311 between the PCa cells. Gene ontology analysis showed that in AR-dependent PCa cells, C-1311 mainly affected the DNA damage response pathways. In contrast, in AR-independent PCa cells, C-1311 targeted the cellular metabolism and inhibited the genes regulating glycolysis and gluconeogenesis. Together, these results indicate that C-1311 warrants further development for the treatment of PCa. Full article
(This article belongs to the Special Issue Biomarkers and Therapy Targets in Urologic Cancer)
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