Renal Cell Carcinoma: From Diagnosis to Identification of Novel Therapeutic Targets and Minimally Invasive Treatments

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 August 2022) | Viewed by 9399

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Division of Urology, European Institute of Oncology-IRCCS, 20141 Milan, Italy
Interests: cancer cells; cancer biology; prostate cancer; urology; prostate; bladder cancer; urologic oncology; cancer metastasis; oncology; doppler ultrasonography
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Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Unit of Oncologic Minimally- Invasive Urology and Andrology, Careggi Hospital, Florence, Italy
Interests: renal cell carcinoma; prostate cancer; bladder cancer; robotic surgery; biomarkers
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Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona- Polo Chirurgico Confortini - Borgo Trento, Verona, Italy
Interests: renal cell carcinoma; prostate cancer; bladder cancer; robotic surgery; biomarkers
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Department of Emergency and Organ Transplantation – Urology, Andrology and Kidney Transplantation Unit - University of Bari « Aldo Moro », 70124 Bari, Italy
Interests: renal cell carcinoma; prostate cancer; bladder cancer
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Department of Emergency and Organ Transplantation – Urology, Andrology and Kidney Transplantation Unit - University of Bari « Aldo Moro », 70124 Bari, Italy
Interests: renal cell carcinoma; prostate cancer; bladder cancer
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Department of Urology, University of Bologna, S-Orsola-Malpighi Hospital, Bologna, Italy
Interests: renal cell carcinoma; prostate cancer; bladder cancer; robotic surgery
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1. Division of Urology, European Institute of Oncology-IRCCS, Milan, Italy
2. Department of Oncology and Haematology-Oncology, Università degli studi di Milano, Milan, Italy
Interests: renal cell carcinoma; prostate cancer; bladder cancer; robotic surgery
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1. Division of Urology, European Institute of Oncology-IRCCS, Milan, Italy
2. Department of Oncology and Haematology-Oncology, Università degli studi di Milano, Milan, Italy
Interests: renal cell carcinoma; prostate cancer; bladder cancer; robotic surgery
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Special Issue Information

Dear Colleagues,

Renal cell carcinoma (RCC) is the most frequent malignancy affecting the adult kidney and the twelfth most common cancer. The pathophysiology of RCC is complex and arises from a combination of gene mutations (i.e., VHL, PBMR1, SETD2, BAP1, etc.) in addition to other factors such as diabetes, obesity, smoking, and hypertension. In the early stages, the disease is frequently asymptomatic and incidentally diagnosed by imaging, having a good prognosis; conversely, RCC has a high mortality rate in advanced phases, due to poor responses to radiotherapy and chemotherapy. The progressive introduction of high-throughput technologies and recent studies of molecular and genomic profiling have shed new light on the pathophysiology of RCC. Moreover, in recent years, there has been a growing interest in identifying tumor markers not only for diagnostic purposes but also to improve the predictive power of clinical and pathological parameters. This Special Issue of Diagnostics aims to collect studies on minimally invasive treatment and translational research for the management and diagnosis of renal cell carcinoma (RCC).

You may choose our Joint Special Issue in Diagnostics.

Dr. Matteo Ferro
Prof. Dr. Andrea Minervini
Prof. Dr. Alessandro Antonelli
Dr. Angelo Porreca
Prof. Giuseppe Lucarelli
Prof. Dr. Michele Battaglia
Prof. Dr. Ditonno Pasquale
Prof. Dr. Riccardo Schiavina
Prof. Dr. Ottavio De Cobelli
Dr. Gennaro Musi
Guest Editors

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Keywords

  • renal cell carcinoma
  • biomarker
  • molecular biology
  • diagnosis
  • prognosis
  • pathology

Published Papers (4 papers)

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Research

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23 pages, 2168 KiB  
Article
Novel Expression of Thymine Dimers in Renal Cell Carcinoma, Demonstrated through Immunohistochemistry
by Dorin Novacescu, Talida Georgiana Cut, Alin Adrian Cumpanas, Felix Bratosin, Raluca Amalia Ceausu and Marius Raica
Biomedicines 2022, 10(11), 2673; https://doi.org/10.3390/biomedicines10112673 - 23 Oct 2022
Cited by 4 | Viewed by 1512
Abstract
Despite significant developments in renal cell carcinoma (RCC) detection and molecular pathology, mortality has been steadily rising. Advanced RCC remains an incurable disease. Better clinical management tools, i.e., RCC biomarkers, have yet to emerge. Thymine-dimers (TDs) were traditionally considered photo-dependent pre-mutagenic lesions, occurring [...] Read more.
Despite significant developments in renal cell carcinoma (RCC) detection and molecular pathology, mortality has been steadily rising. Advanced RCC remains an incurable disease. Better clinical management tools, i.e., RCC biomarkers, have yet to emerge. Thymine-dimers (TDs) were traditionally considered photo-dependent pre-mutagenic lesions, occurring exclusively during ultra-violet light exposure. Non-oxidative, direct, and preferential byproducts of DNA photochemical reactions, TDs, have recently shown evidence regarding UVR-independent formation. In this study, we investigate, for the first time, TD expression within RCC tumor tissue and tumor-adjacent healthy renal parenchyma using a TD-targeted IHC monoclonal antibody, clone KTM53. Remarkably, out of the 54 RCCs evaluated, 77.8% showed nuclear TD-expression in RCC tumor tissue and 37% in the tumor-adjacent healthy renal parenchyma. A comprehensive report regarding quantitative/qualitative TD-targeted immunostaining was elaborated. Two main distribution models for TD expression within RCC tumor tissue were identified. Statistical analysis showed significant yet moderate correlations regarding TD-positivity in RCC tissue/tumor-adjacent healthy renal parenchyma and TNM stage at diagnosis/lymphatic dissemination, respectively, indicating possible prognostic relevance. We review possible explanations for UVR-independent TD formation and molecular implications regarding RCC carcinogenesis. Further rigorous molecular analysis is required in order to fully comprehend/validate the biological significance of this newly documented TD expression in RCC. Full article
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28 pages, 3641 KiB  
Article
Evaluating Established Roles, Future Perspectives and Methodological Heterogeneity for Wilms’ Tumor 1 (WT1) Antigen Detection in Adult Renal Cell Carcinoma, Using a Novel N-Terminus Targeted Antibody (Clone WT49)
by Dorin Novacescu, Talida Georgiana Cut, Alin Adrian Cumpanas, Silviu Constantin Latcu, Razvan Bardan, Ovidiu Ferician, Cosmin-Ciprian Secasan, Andrei Rusmir and Marius Raica
Biomedicines 2022, 10(4), 912; https://doi.org/10.3390/biomedicines10040912 - 15 Apr 2022
Cited by 5 | Viewed by 2851
Abstract
Renal cell carcinoma (RCC) is arguably the deadliest form of genitourinary malignancy and is nowadays viewed as a heterogeneous series of cancers, with the same origin but fundamentally different metabolisms and clinical behaviors. Immunohistochemistry (IHC) is increasingly necessary for RCC subtyping and definitive [...] Read more.
Renal cell carcinoma (RCC) is arguably the deadliest form of genitourinary malignancy and is nowadays viewed as a heterogeneous series of cancers, with the same origin but fundamentally different metabolisms and clinical behaviors. Immunohistochemistry (IHC) is increasingly necessary for RCC subtyping and definitive diagnosis. WT1 is a complex gene involved in carcinogenesis. To address reporting heterogeneity and WT1 IHC standardization, we used a recent N-terminus targeted monoclonal antibody (clone WT49) to evaluate WT1 protein expression in 56 adult RCC (aRCC) cases. This is the largest WT1 IHC investigation focusing exclusively on aRCCs and the first report on clone WT49 staining in aRCCs. We found seven (12.5%) positive cases, all clear cell RCCs, showing exclusively nuclear staining for WT1. We did not disregard cytoplasmic staining in any of the negative cases. Extratumoral fibroblasts, connecting tubules and intratumoral endothelial cells showed the same exclusively nuclear WT1 staining pattern. We reviewed WT1 expression patterns in aRCCs and the possible explanatory underlying metabolomics. For now, WT1 protein expression in aRCCs is insufficiently investigated, with significant discrepancies in the little data reported. Emerging WT1-targeted RCC immunotherapy will require adequate case selection and sustained efforts to standardize the quantification of tumor-associated antigens for aRCC and its many subtypes. Full article
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Review

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32 pages, 459 KiB  
Review
Contemporary Clinical Definitions, Differential Diagnosis, and Novel Predictive Tools for Renal Cell Carcinoma
by Dorin Novacescu, Bogdan Ovidiu Feciche, Alin Adrian Cumpanas, Razvan Bardan, Andrei Valentin Rusmir, Yahya Almansour Bitar, Vlad Ilie Barbos, Talida Georgiana Cut, Marius Raica and Silviu Constantin Latcu
Biomedicines 2022, 10(11), 2926; https://doi.org/10.3390/biomedicines10112926 - 14 Nov 2022
Cited by 6 | Viewed by 1928
Abstract
Despite significant progress regarding clinical detection/imaging evaluation modalities and genetic/molecular characterization of pathogenesis, advanced renal cell carcinoma (RCC) remains an incurable disease and overall RCC mortality has been steadily rising for decades. Concomitantly, clinical definitions have been greatly nuanced and refined. RCCs are [...] Read more.
Despite significant progress regarding clinical detection/imaging evaluation modalities and genetic/molecular characterization of pathogenesis, advanced renal cell carcinoma (RCC) remains an incurable disease and overall RCC mortality has been steadily rising for decades. Concomitantly, clinical definitions have been greatly nuanced and refined. RCCs are currently viewed as a heterogeneous series of cancers, with the same anatomical origin, but fundamentally different metabolisms and clinical behaviors. Thus, RCC pathological diagnosis/subtyping guidelines have become increasingly intricate and cumbersome, routinely requiring ancillary studies, mainly immunohistochemistry. Meanwhile, RCC-associated-antigen targeted systemic therapy has been greatly diversified and emerging, novel clinical applications for RCC immunotherapy have already reported significant survival benefits, at least in the adjuvant setting. Even so, systemically disseminated RCCs still associate very poor clinical outcomes, with currently available therapeutic modalities only being able to prolong survival. In lack of a definitive cure for advanced RCCs, integration of the amounting scientific knowledge regarding RCC pathogenesis into RCC clinical management has been paramount for improving patient outcomes. The current review aims to offer an integrative perspective regarding contemporary RCC clinical definitions, proper RCC clinical work-up at initial diagnosis (semiology and multimodal imaging), RCC pathological evaluation, differential diagnosis/subtyping protocols, and novel clinical tools for RCC screening, risk stratification and therapeutic response prediction. Full article

Other

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12 pages, 557 KiB  
Systematic Review
Micro-RNAs Predict Response to Systemic Treatments in Metastatic Renal Cell Carcinoma Patients: Results from a Systematic Review of the Literature
by Martina Monti, Susanna Lunardini, Igino Andrea Magli, Riccardo Campi, Giulia Primiceri, Francesco Berardinelli, Daniele Amparore, Daniela Terracciano, Giuseppe Lucarelli, Luigi Schips, Matteo Ferro and Michele Marchioni
Biomedicines 2022, 10(6), 1287; https://doi.org/10.3390/biomedicines10061287 - 31 May 2022
Cited by 11 | Viewed by 2186
Abstract
Locally advanced or metastatic renal cell carcinomas (mRCCs) account for up to 15% of all kidney cancer diagnoses. Systemic therapies (with or without surgery) represent gold standard treatments, mostly based on tyrosine kinase inhibitors in association with immunotherapy. We provide an overview of [...] Read more.
Locally advanced or metastatic renal cell carcinomas (mRCCs) account for up to 15% of all kidney cancer diagnoses. Systemic therapies (with or without surgery) represent gold standard treatments, mostly based on tyrosine kinase inhibitors in association with immunotherapy. We provide an overview of the current knowledge of miRNAs as predictors of treatment resistance. A systematic review of the literature was carried out in January 2022 following the PICO methodology. Overall, we included seven studies—four testing plasmatic miRNAs, two exosomal miRNAs, and one urinary miRNA. A total of 789 patients were included (354 for plasmatic miRNAs, 366 for urinary miRNAs, and 69 for exosomal miRNAs). Several miRNAs were tested within the included studies, but six plasmatic (miR9-5-p¸ miR-192, miR193-3p, miR-501-3p¸ miR-221, miR-376b-3p) one urinary (miR-30a-5p), and three exosomal (miR-35-5p, miR-301a-3p, miR-1293) were associated with resistance to systemic treatments or treatment failure in mRCC patients. Results showed a fair accuracy of these biomarkers in predicting treatment resistance and overall survival. However, to date, the biomarkers tested have not been validated and their clinical uses are not recommended. Nevertheless, the literature results are encouraging; future large clinical trials are warranted to validate the effectiveness of these tools in clinical decision-making. Full article
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