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Bladder Cancer and Personalized Treatment
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Bladder Cancer and Personalized Treatment

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 13543

Special Issue Editors

Dr. Tahlita C. M. Zuiverloon

E-Mail Website
Guest Editor
Department of Urology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
Interests: treatment resistance mechanisms in BCG-unresponsive nonmuscle invasive bladder cancer; pharmacogenomics; urinary diagnostics; chemotherapy resistance mechanisms in muscle-invasive bladder cancer
Dr. Markus Eckstein

E-Mail Website
Co-Guest Editor
Institute of Pathology, University Hospital Erlangen, 91052 Erlangen, Germany
Interests: tumor immunology; intrinsic subtypes; immune therapy
Dr. Astrid A.M. van der Veldt

E-Mail Website
Co-Guest Editor
Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
Interests: immunotherapy and imaging therapy; urothelial cell carcinoma; renal cell carcinoma

Special Issue Information

Dear Colleagues,

The integration of various “omics” technologies for investigating the genetic and genomic make-up of bladder cancer has improved our understanding of the molecular tumor biology and continues to contribute to the development of more personalized treatment approaches. Different molecular subtypes have been identified in (non)muscle invasive bladder cancer; the presence of tumor heterogeneity has been identified as a source of treatment resistance, and molecular tumor make-up is now being evaluated in different clinical studies as a predictor of treatment response.

This Special Issue of the Journal of Personalized Medicine aims to highlight the current state of science and showcase some of the latest findings in the field of bladder omics. The topics include studies that investigate molecular biomarkers of response to treatment and radiomics to improve staging in muscle-invasive bladder cancer.

Dr. Tahlita C.M. Zuiverloon
Guest Editor

Dr. Markus Eckstein
Dr. Astrid A.M. van der Veldt
Co-Guest Editors

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. Journal of Personalized Medicine 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

  • Urothelial carcinoma
  • Biomarkers
  • Genomics
  • Targeted therapy
  • Radiomics
  • Molecular subtypes

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Published Papers (4 papers)

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Research

12 pages, 1943 KiB  
Article
Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations
by Ekaterina Laukhtina, Ursula Lemberger, Andreas Bruchbacher, Dafina Ilijazi, Stephan Korn, Florian Berndl, David D’Andrea, Martin Susani, Dmitry Enikeev, Eva Compérat, Shahrokh F. Shariat and Melanie R. Hassler
J. Pers. Med. 2021, 11(11), 1147; https://doi.org/10.3390/jpm11111147 - 4 Nov 2021
Cited by 3 | Viewed by 2323
Abstract
The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate [...] Read more.
The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate KMT2D expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in KMT2D exons. Cox regression was used to assess the relationship of KMT2D protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, p = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic KMT2D variants and tumor location (p = 0.02). Pathogenic KMT2D variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic KMT2D alterations. Both IHC and NGS analyses of KMT2D failed to detect a statistically significant association between KMT2D protein or KMT2D gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all p > 0.05). KMT2D alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and KMT2D mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy. Full article
(This article belongs to the Special Issue Bladder Cancer and Personalized Treatment)
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14 pages, 996 KiB  
Article
Survival Impact of Current-Smoking-Related COPD or COPD with Acute Exacerbation on Bladder Preservation through Concurrent Chemoradiotherapy for Muscle-Invasive Bladder Urothelial Carcinoma
by Jiaqiang Zhang, Shyh-Chyi Chang, Ming-Feng Chiang, Kuo-Chin Chiu and Szu-Yuan Wu
J. Pers. Med. 2021, 11(10), 958; https://doi.org/10.3390/jpm11100958 - 26 Sep 2021
Cited by 3 | Viewed by 2320
Abstract
PURPOSE: The survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving concurrent chemoradiotherapy (CCRT) for bladder preservation is unclear. METHODS: We recruited patients with MIBUC, clinical stages IIA–IVB, [...] Read more.
PURPOSE: The survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving concurrent chemoradiotherapy (CCRT) for bladder preservation is unclear. METHODS: We recruited patients with MIBUC, clinical stages IIA–IVB, who had received maximal transurethral resection of bladder tumor (TURBT) followed by CCRT from the Taiwan Cancer Registry Database. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into two groups by using propensity score matching based on the preexisting COPD status (within 1 year before CCRT) to compare overall survival outcomes: Group 1 (never smokers without COPD) and Group 2 (current smokers with COPD). RESULTS: In multivariate Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality in Group 2 compared with Group 1 was 1.89 (1.12–3.18), p = 0.017. The aHRs (95% CIs) of all-cause mortality for ≥1 and ≥2 hospitalizations for COPDAE within 1 year before CCRT for bladder preservation were 3.26 (1.95–5.46) and 6.33 (3.55–11.281) compared with non-COPDAE patients with MIBUC undergoing CCRT for bladder preservation. CONCLUSIONS: Among patients with MIBUC undergoing TURBT followed by CCRT for bladder preservation, current smokers with smoking-related COPD had worse survival outcomes than did nonsmokers without COPD. CONDENSED ABSTRACT: This was the first study to estimate the survival impact of smoking-related chronic obstructive pulmonary disease (COPD) on patients with muscle-invasive bladder urothelial carcinoma (MIBUC) receiving maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy (CCRT) for bladder preservation. Smoking-related COPD was a significant independent risk factor for all-cause mortality in patients with clinical stages IIA–IVB receiving TURBT followed by CCRT. Hospitalization frequency for COPD with at least one acute exacerbation within 1 year before CCRT was highly associated with high mortality for patients with MIBUC receiving CCRT for bladder preservation. Not only all-cause death but also bladder cancer death and COPD death were significantly higher in the current-smoking COPD group than in the never-smoking non-COPD group. Full article
(This article belongs to the Special Issue Bladder Cancer and Personalized Treatment)
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13 pages, 769 KiB  
Article
KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer
by Hendrik Jütte, Moritz Reike, Ralph M. Wirtz, Maximilian Kriegmair, Philipp Erben, Karl Tully, Veronika Weyerer, Markus Eckstein, Arndt Hartmann, Sebastian Eidt, Felix Wezel, Christian Bolenz, Andrea Tannapfel, Joachim Noldus and Florian Roghmann
J. Pers. Med. 2021, 11(6), 473; https://doi.org/10.3390/jpm11060473 - 26 May 2021
Cited by 9 | Viewed by 3387
Abstract
Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival, especially those with pathological complete response (pCR). The response to NAC according to molecular subtypes has been discussed. Molecular targets such as estrogen [...] Read more.
Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival, especially those with pathological complete response (pCR). The response to NAC according to molecular subtypes has been discussed. Molecular targets such as estrogen receptor (ESR1) and human epidermal growth factor receptor 2 (ERBB2) play an important role in breast cancer management and have also been associated with urothelial bladder cancer. Hence, the association of Keratin 20 (KRT20) Keratin 5 (KRT5), ESR1, and ERBB2 mRNA expression in MIBC at transurethral resection (TUR-BT) with pCR after NAC was analyzed retrospectively. Formalin-fixed paraffin-embedded tumour tissue samples from TUR-BT of 54 patients (42 males, 12 females, median age of 64) with MIBC were analyzed for KRT20, KRT5, ESR1, and ERBB2 mRNA expression. After NAC, RC was performed, and the specimens were evaluated for pCR. Statistical analyses comprised nonparametric and chi2 testing, partition models, and Spearman correlation analyses. After NAC, 22 out of 54 patients (40.7%) had pCR. Tumours with an elevated expression of markers associated with luminal differentiation (KRT20, ERBB2, ESR1) were associated with a higher chance of pCR (55% vs. 15.8%, p = 0.009). Elevated ERBB2 expression was positively correlated with luminal expression features such as KRT20, and negatively with basal characteristics such as KRT5. Patients with MIBC showing a high expression of ERBB2, ESR1, or KRT20 have a significantly higher chance of pCR following NAC. These findings might improve patient selection for NAC in MIBC. Full article
(This article belongs to the Special Issue Bladder Cancer and Personalized Treatment)
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15 pages, 2344 KiB  
Article
Combination of Talazoparib and Palbociclib as a Potent Treatment Strategy in Bladder Cancer
by Florian G. Klein, Charlène Granier, Yuling Zhao, Qi Pan, Zhichao Tong, Jürgen E. Gschwend, Per Sonne Holm and Roman Nawroth
J. Pers. Med. 2021, 11(5), 340; https://doi.org/10.3390/jpm11050340 - 24 Apr 2021
Cited by 12 | Viewed by 4317
Abstract
The use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors represents a potent strategy for cancer therapy. Due to the complex molecular network that regulates cell cycle progression, cancer cells often acquire resistance mechanisms against these inhibitors. Previously, our group identified molecular factors conferring resistance [...] Read more.
The use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors represents a potent strategy for cancer therapy. Due to the complex molecular network that regulates cell cycle progression, cancer cells often acquire resistance mechanisms against these inhibitors. Previously, our group identified molecular factors conferring resistance to CDK4/6 inhibition in bladder cancer (BLCA) that also included components within the DNA repair pathway. In this study, we validated whether a combinatory treatment approach of the CDK4/6 inhibitor Palbociclib with Poly-(ADP-Ribose) Polymerase (PARP) inhibitors improves therapy response in BLCA. First, a comparison of PARP inhibitors Talazoparib and Olaparib showed superior efficacy of Talazoparib in vitro and displayed high antitumor activity in xenografts in the chicken chorioallantoic membrane (CAM) model. Moreover, the combination of Talazoparib and the CDK4/6 inhibitor Palbociclib synergistically reduced tumor growth in Retinoblastoma protein (RB)-positive BLCA in vitro and in a CAM model, an effect that relies on Palbociclib-induced cell cycle arrest in G0/G1-phase complemented by a G2 arrest induced by Talazoparib. Interestingly, Talazoparib-induced apoptosis was reduced by Palbociclib. The combination of Palbociclib and Talazoparib effectively enhances BLCA therapy, and RB is a molecular biomarker of response to this treatment regimen. Full article
(This article belongs to the Special Issue Bladder Cancer and Personalized Treatment)
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