Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

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

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 29336

Share This Special Issue

Special Issue Editors

Dr. Albert Font

E-Mail Website
Guest Editor

Badalona–Badalona Applied Research Group in Oncology (B·ARGO), Catalan Institute of Oncology, 08916 Badalona, Spain
Interests: genitourinary tumors
Special Issues, Collections and Topics in MDPI journals

Dr. Vicenç Ruiz de Porras

E-Mail Website
Guest Editor

1. Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (B·ARGO), Ctra. Can Ruti-Camí de les Escoles s/n, 08916 Badalona, Spain
2. Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain
Interests: metastatic prostate cancer; bladder cancer; therapy resistance; chemotherapy; predictive biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Urological tumors comprise bladder, prostate, renal, upper urinary tract, and germ-cell tumors, among others. The incidence of urological tumors has increased significantly over the past 40 years. In fact, all of them rank in the top ten list of human cancers and account for up to 33% of malignancies affecting the male population. Their different pathogenetic mechanisms and their varied diagnostic and therapeutic approaches represent a challenge in clinical practice. Thus, treatment for urologic cancers depends on several factors, such as the tumor’s grade and stage. Common options include surgery, chemotherapy, and radiation therapy.

However, although the therapeutic landscape of urological tumors has significantly improved in recent years with the incorporation of new treatment options such as immunotherapy and target therapies, understanding the molecular mechanisms of tumor progression and therapy resistance will help us to develop novel treatment strategies and predict drug response toward precision medicine.

This Special Issue of the International Journal of Molecular Sciences therefore encompasses original and review articles on the molecular mechanisms leading to tumor progression and resistance to current treatment options, new therapeutic strategies, as well as new prognostic and predictive biomarkers for urological tumors.

Dr. Albert Font Pous
Dr. Vicenç Ruiz de Porras
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
bladder cancer
renal cell carcinoma
upper urinary tract tumors
testicular cancer
predictive and prognostic biomarkers
tumor progression
novel treatment strategies
chemotherapy
immunotherapy
target therapies
drug resistance mechanisms
tumor microenvironment
precision medicine

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (10 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research, Review

5 pages, 219 KiB

Open AccessEditorial

Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers

by Vicenç Ruiz de Porras and Albert Font

Int. J. Mol. Sci. 2023, 24(21), 15795; https://doi.org/10.3390/ijms242115795 - 31 Oct 2023

Cited by 1 | Viewed by 1115

Abstract

Urological cancer encompasses a diverse range of tumors, including bladder, prostate, renal, upper urinary tract, and germ cell tumors [...] Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

Research

Jump to: Editorial, Review

20 pages, 3582 KiB

Open AccessArticle

An In Vitro Analysis of TKI-Based Sequence Therapy in Renal Cell Carcinoma Cell Lines

by Angela Zaccagnino, Bozhena Vynnytska-Myronovska, Michael Stöckle and Kerstin Junker

Int. J. Mol. Sci. 2023, 24(6), 5648; https://doi.org/10.3390/ijms24065648 - 15 Mar 2023

Cited by 3 | Viewed by 2487

Abstract

The tyrosine kinase inhibitor (TKI) cabozantinib might impede the growth of the sunitinib-resistant cell lines by targeting MET and AXL overexpression in metastatic renal cell carcinoma (mRCC). We studied the role of MET and AXL in the response to cabozantinib, particularly following long-term administration with sunitinib. Two sunitinib-resistant cell lines, 786-O/S and Caki-2/S, and the matching 786-O/WT and Caki-2/WT cells were exposed to cabozantinib. The drug response was cell-line-specific. The 786-O/S cells were less growth-inhibited by cabozantinib than 786-O/WT cells (p-value = 0.02). In 786-O/S cells, the high level of phosphorylation of MET and AXL was not affected by cabozantinib. Despite cabozantinib hampering the high constitutive phosphorylation of MET, the Caki-2 cells showed low sensitivity to cabozantinib, and this was independent of sunitinib pretreatment. In both sunitinib-resistant cell lines, cabozantinib increased Src-FAK activation and impeded mTOR expression. The modulation of ERK and AKT was cell-line-specific, mirroring the heterogeneity among the patients. Overall, the MET- and AXL-driven status did not affect cell responsiveness to cabozantinib in the second-line treatment. The activation of Src-FAK might counteract cabozantinib activity and contribute to tumor survival and may be considered an early indicator of therapy response. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Figure 1

22 pages, 5340 KiB

Open AccessArticle

Stress-Inducible SCAND Factors Suppress the Stress Response and Are Biomarkers for Enhanced Prognosis in Cancers

by Mona Sheta, Kunihiro Yoshida, Hideka Kanemoto, Stuart K. Calderwood and Takanori Eguchi

Int. J. Mol. Sci. 2023, 24(6), 5168; https://doi.org/10.3390/ijms24065168 - 8 Mar 2023

Cited by 5 | Viewed by 2869

Abstract

The cell stress response is an essential system present in every cell for responding and adapting to environmental stimulations. A major program for stress response is the heat shock factor (HSF)–heat shock protein (HSP) system that maintains proteostasis in cells and promotes cancer progression. However, less is known about how the cell stress response is regulated by alternative transcription factors. Here, we show that the SCAN domain (SCAND)-containing transcription factors (SCAN-TFs) are involved in repressing the stress response in cancer. SCAND1 and SCAND2 are SCAND-only proteins that can hetero-oligomerize with SCAN-zinc finger transcription factors, such as MZF1(ZSCAN6), for accessing DNA and transcriptionally co-repressing target genes. We found that heat stress induced the expression of SCAND1, SCAND2, and MZF1 bound to HSP90 gene promoter regions in prostate cancer cells. Moreover, heat stress switched the transcript variants’ expression from long noncoding RNA (lncRNA-SCAND2P) to protein-coding mRNA of SCAND2, potentially by regulating alternative splicing. High expression of HSP90AA1 correlated with poorer prognoses in several cancer types, although SCAND1 and MZF1 blocked the heat shock responsiveness of HSP90AA1 in prostate cancer cells. Consistent with this, gene expression of SCAND2, SCAND1, and MZF1 was negatively correlated with HSP90 gene expression in prostate adenocarcinoma. By searching databases of patient-derived tumor samples, we found that MZF1 and SCAND2 RNA were more highly expressed in normal tissues than in tumor tissues in several cancer types. Of note, high RNA expression of SCAND2, SCAND1, and MZF1 correlated with enhanced prognoses of pancreatic cancer and head and neck cancers. Additionally, high expression of SCAND2 RNA was correlated with better prognoses of lung adenocarcinoma and sarcoma. These data suggest that the stress-inducible SCAN-TFs can function as a feedback system, suppressing excessive stress response and inhibiting cancers. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Figure 1

18 pages, 1025 KiB

Open AccessArticle

The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis

by Anna Andrzejczak, Krzysztof Tupikowski, Anna Tomkiewicz, Bartosz Małkiewicz, Kuba Ptaszkowski, Aleksandra Domin, Tomasz Szydełko and Lidia Karabon

Int. J. Mol. Sci. 2023, 24(3), 2042; https://doi.org/10.3390/ijms24032042 - 20 Jan 2023

Cited by 5 | Viewed by 2238

Abstract

Renal cell cancer is the most common type of kidney cancer in adults, and clear cell renal cell carcinoma (ccRCC) is the most diagnosed type. T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) belongs to immunological checkpoints that are key regulators of the immune response. One of the known TIM-3 ligands is galectin-9 (LGALS9). A limited number of studies have shown an association between TIM-3 polymorphisms and cancer risk in the Asian population; however, there is no study on the role of LGALS9 polymorphisms in cancer. The present study aimed to analyze the influence of TIM-3 and LGALS9 polymorphisms on susceptibility to ccRCC and patient overall survival (OS), with over ten years of observations. Using TaqMan probes, ARMS–PCR, and RFPL-PCR, we genotyped two TIM-3 single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four LGALS9 SNPs: rs361497, rs3751093, rs4239242, and rs4794976. We found that the presence of the rs10057302 A allele (AC + AA genotypes) as well as the rs4794976 T allele (GT + TT genotypes) decreased susceptibility to ccRCC by two-fold compared to corresponding homozygotes. A subgroup analysis showed the association of some SNPs with clinical features. Moreover, TIM-3 rs1036199 significantly influenced OS. Our results indicate that variations within TIM-3 and LGALS9 genes are associated with ccRCC risk and OS. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Figure 1

15 pages, 2092 KiB

Open AccessArticle

Mutational Landscape of Bladder Cancer in Mexican Patients: KMT2D Mutations and chr11q15.5 Amplifications Are Associated with Muscle Invasion

by María D. Pérez-Montiel, Dennis Cerrato-Izaguirre, Yesennia Sánchez-Pérez, Jose Diaz-Chavez, Carlo César Cortés-González, Jairo A. Rubio, Miguel A. Jiménez-Ríos, Luis A. Herrera, Anna Scavuzzo, Abelardo Meneses-García, Ricardo Hernández-Martínez, Felipe Vaca-Paniagua, Andrea Ramírez, Alicia Orozco, David Cantú-de-León and Diddier Prada

Int. J. Mol. Sci. 2023, 24(2), 1092; https://doi.org/10.3390/ijms24021092 - 6 Jan 2023

Cited by 2 | Viewed by 3121

Abstract

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute—Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and exome sequenced. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Figure 1

14 pages, 3722 KiB

Open AccessArticle

Claudin-3 Loss of Expression Is a Prognostic Marker in Castration-Resistant Prostate Cancer

by María J. Orea, Javier C. Angulo, Ana González-Corpas, David Echegaray, Marcos Marvá, María V. T. Lobo, Begoña Colás and Santiago Ropero

Int. J. Mol. Sci. 2023, 24(1), 803; https://doi.org/10.3390/ijms24010803 - 2 Jan 2023

Cited by 9 | Viewed by 3518

Abstract

Castration-resistant prostate cancer (CRPC) development is the foremost concern after treatment of patients with high risk with locally advanced or metastatic prostate cancer. Androgen receptor (AR) is the main driver of CRPC development, through its interaction with epigenetic modifier genes, placing epigenetics modifications in the forefront of CRPC development. Comparing the DNA methylation and expression profile of androgen-sensitive and -refractory prostate cancer cells, we describe the epigenetic silencing of claudin-3 (CLDN3) in AR positive cells resistant to androgen deprivation (LNCaP-abl). CLDN3 silencing was associated with DNA methylation, loss of histone acetylation and H3K27 methylation, and was re-expressed by the combined treatment with the epigenetic modulators Aza and SAHA. From a functional point of view, CLDN3 loss was associated with increased cellular invasion. Immunohistochemical analysis showed decreased CLDN3 expression in samples from CRPC patients. Interestingly, CLDN3 expression was significantly decreased in samples from patients with high total Gleason score (≥8) and locally advanced tumors. Finally, CLDN3 loss of expression was associated with worse disease-free survival and time to clinical progression. In conclusion, our findings strongly indicate that epigenetic silencing of CLDN3 is a common event in CRPC that could be useful as a molecular marker for the prognosis of prostate cancer patients and to discriminate aggressive from indolent prostate tumors. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Figure 1

11 pages, 1223 KiB

Open AccessArticle

Tumor-Microenvironment Characterization of the MB49 Non-Muscle-Invasive Bladder-Cancer Orthotopic Model towards New Therapeutic Strategies

by Sonia Domingos-Pereira, Karthik Sathiyanadan, Lenka Polak, Jacques-Antoine Haefliger, Martina Schmittnaegel, Carola H. Ries, Patrice Jichlinski, Beat Roth, Laurent Derré and Denise Nardelli-Haefliger

Int. J. Mol. Sci. 2023, 24(1), 123; https://doi.org/10.3390/ijms24010123 - 21 Dec 2022

Cited by 7 | Viewed by 4331

Abstract

Bacillus Calmette-Guérin (BCG) instillations for the treatment of non-muscle-invasive bladder cancer patients can result in significant side effects and treatment failure. Immune checkpoint blockade and/or decreasing tumor-infiltrating myeloid suppressor cells may be alternative or complementary treatments. Here, we have characterized immune cell infiltration and chemoattractant molecules in mouse orthotopic MB49 bladder tumors. Our data show a 100-fold increase in CD45⁺ immune cells from day 5 to day 9 tumors including T cells and mainly myeloid cells. Both monocytic myeloid-derived suppressor-cells (M-MDSC) and polymorphonuclear (PMN)-MDSC were strongly increased in day 9 tumors, with PMN-MDSC representing ca. 70% of the myeloid cells in day 12 tumors, while tumor associated macrophages (TAM) were only modestly increased. The kinetic of PD-L1 tumor expression correlated with published data from patients with PD-L1 expressing bladder tumors and with efficacy of anti-PD-1 treatment, further validating the orthotopic MB49 bladder-tumor model as suitable for designing novel therapeutic strategies. Comparison of chemoattractants expression during MB49 bladder tumors grow highlighted CCL8 and CCL12 (CCR2-ligands), CCL9 and CCL6 (CCR-1-ligands), CXCL2 and CXCL5 (CXCR2-ligands), CXCL12 (CXCR4-ligand) and antagonist of C5/C5a as potential targets to decrease myeloid suppressive cells. Data obtained with a single CCR2 inhibitor however showed that the complex chemokine crosstalk would require targeting multiple chemokines for anti-tumor efficacy. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Figure 1

14 pages, 2679 KiB

Open AccessArticle

TOLLIP Protein Expression Predicts Unfavorable Outcome in Renal Cell Carcinoma

by Adam Kowalewski, Damian Jaworski, Jędrzej Borowczak, Mateusz Maniewski, Krzysztof Szczerbowski, Paulina Antosik, Justyna Durślewicz, Marta Smolińska, Joanna Ligmanowska, Dariusz Grzanka and Łukasz Szylberg

Int. J. Mol. Sci. 2022, 23(23), 14702; https://doi.org/10.3390/ijms232314702 - 25 Nov 2022

Cited by 5 | Viewed by 2336

Abstract

Resistance to systemic therapy is one of the hallmarks of renal cell carcinoma (RCC). Recently, TOLLIP has emerged as a possible driver of autophagy and chemoresistance. We explored the relationship between primary and metastatic RCC tumor characteristics, patient survival, and TOLLIP expression. The tissue microarrays cohort contained 95 cores of the primary tumor, matched metastases, and matched adjacent tissues derived from 32 RCC patients. TOLLIP expression in tumor samples was evaluated using the H-score. All examined samples showed cytoplasmic TOLLIP expression, with a median value of 100 in primary tumors, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to primary or metastatic RCC (p < 0.05). We found a positive correlation between expressions of TOLLIP in the primary tumor and its metastases (p < 0.05; k = 0.48). TOLLIP expression significantly correlates with a lower overall survival rate (p = 0.047). TOLLIP functions as a ubiquitin-LC3 adaptor in the intracellular pathway associated with autophagy. Relative TOLLIP overexpression may augment autophagy-related signaling, limiting susceptibility to therapy. The blockade of TOLLIP physiological function seems to be a promising approach to overcoming resistance to systemic therapy. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Figure 1

9 pages, 12410 KiB

Open AccessArticle

Antitumor Effects of Orally Administered Rare Sugar D-Allose in Bladder Cancer

by Yoichiro Tohi, Rikiya Taoka, Xia Zhang, Yuki Matsuoka, Akihide Yoshihara, Emi Ibuki, Reiji Haba, Kazuya Akimitsu, Ken Izumori, Yoshiyuki Kakehi and Mikio Sugimoto

Int. J. Mol. Sci. 2022, 23(12), 6771; https://doi.org/10.3390/ijms23126771 - 17 Jun 2022

Cited by 11 | Viewed by 2535

Abstract

D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (TXNIP) expression and affect the production of intracellular reactive oxygen species (ROS). However, the antitumor effect of D-allose is unknown. This study aimed to determine whether orally administered D-allose could be a candidate drug against bladder cancer (BC). To this end, BC cell lines were treated with varying concentrations of D-allose (10, 25, and 50 mM). Cell viability and intracellular ROS levels were assessed using cell viability assay and flow cytometry. TXNIP expression was evaluated using Western blotting. The antitumor effect of orally administered D-allose was assessed using a xenograft mouse model. D-allose reduced cell viability and induced intracellular ROS production in BC cells. Moreover, D-allose stimulated TXNIP expression in a dose-dependent manner. Co-treatment of D-allose and the antioxidant L-glutathione canceled the D-allose-induced reduction in cell viability and intracellular ROS elevation. Furthermore, oral administration of D-allose inhibited tumor growth without adverse effects (p < 0.05). Histopathological findings in tumor tissues showed that D-allose decreased the nuclear fission rate from 4.1 to 1.1% (p = 0.004). Oral administration of D-allose suppressed BC growth in a preclinical mouse model, possibly through up-regulation of TXNIP expression followed by an increase in intracellular ROS. Therefore, D-allose is a potential therapeutic compound for the treatment of BC. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

19 pages, 780 KiB

Open AccessReview

The Role of Long Noncoding RNA (lncRNAs) Biomarkers in Renal Cell Carcinoma

by Jacek Rysz, Tomasz Konecki, Beata Franczyk, Janusz Ławiński and Anna Gluba-Brzózka

Int. J. Mol. Sci. 2023, 24(1), 643; https://doi.org/10.3390/ijms24010643 - 30 Dec 2022

Cited by 19 | Viewed by 3886

Abstract

Renal cell carcinoma is one of the common cancers whose incidence and mortality are continuously growing worldwide. Initially, this type of tumour is usually asymptomatic. Due to the lack of reliable diagnostic markers, one-third of ccRCC patients already have distant metastases at the time of diagnosis. This underlines the importance of establishing biomarkers that would enable the prediction of the disease’s course and the risk of metastasis. LncRNA, which modulates genes at the epigenetic, transcriptional, and post-transcriptional levels, appears promising. The actions of lncRNA involve sponging and sequestering target miRNAs, thus affecting numerous biological processes. Studies have confirmed the involvement of RNAs in various diseases, including RCC. In this review, we focused on MALAT1 (a marker of serious pathological changes and a factor in the promotion of tumorigenesis), RCAT1 (tumour promoter in RCC), DUXAP9 (a plausible marker of localized ccRCC), TCL6 (exerting tumour-suppressive effects in renal cancer), LINC00342 (acting as an oncogene), AGAP2 Antisense1 (plausible predictor of RCC progression), DLEU2 (factor promoting tumours growth via the regulation of epithelial-mesenchymal transition), NNT-AS1 (sponge of miR-22 contributing to tumour progression), LINC00460 (favouring ccRCC development and progression) and Lnc-LSG1 (a factor that may stimulate ccRCC metastasis). Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers)

► Show Figures

Journal Menu

Journal Browser

Molecular Mechanisms of Tumor Progression and New Therapeutic Strategies for Urological Cancers

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (10 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI