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Topical Collection "Clear Cell Renal Cell Carcinoma 2022–2023"

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Published Papers

A topical collection in Cancers (ISSN 2072-6694). This collection belongs to the section "Cancer Pathophysiology".

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Editors

Dr. José I. López

E-Mail Website
Collection Editor

Biocruces-Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Interests: translational uropathology; pathological diagnosis; basic fundamentals of tumor biology
Special Issues, Collections and Topics in MDPI journals

Dr. Claudia Manini

E-Mail Website
Collection Editor

1. Department of Pathology, San Giovanni Bosco Hospital, 10154 Turin, Italy
2. Department of Sciences of Public Health and Pediatrics, University of Turin, 10124 Turin, Italy
Interests: urogenital and neurosurgical pathology
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Clear cell renal cell carcinoma is one of the most interesting areas of study in oncology right now. Despite the advances obtained, this tumor continues to be a health problem of major concern in Western societies, affecting very seriously their public health services. Several characteristics of this tumor make it an exciting meeting point for translational collaboration between clinicians and basic researchers.

Clear cell renal cell carcinoma is a paradigmatic example of inter- and intra-tumor heterogeneity from morphological, immunohistochemical, and molecular viewpoints. It is also a model to study hypoxia-related carcinogenesis. The latest findings on the spatial and temporal evolutionary patterns detected in this tumor are opening up new promising possibilities for more successful treatments. In addition, the identification of metastatic phenotypes will allow the early detection of aggressive genotypes guiding specific patient management.

This tumor is also a good example to investigate the complexity of tumor/tumor and tumor/environment relationships from an ecological perspective. A deeper identification of the varied internal tumor self-organization through the specialization of cell clones and subclones as local invaders and metastasizers, on one hand, and the interactions of specific subsets of tumor cells with the local host microenvironment, on the other, will enrich significantly our knowledge of this neoplasm. Finally, alternative approaches such as game theory have provided, in recent years, promising mathematical models to unveil the diversity of possible behaviors of this polyedrical disease.

Clear cell renal cell carcinoma is also a paradigmatic test bench for antiangiogenic and immune checkpoint blockage therapies. The refinement of these therapeutic tools administered alone or in combination is a hot issue in oncology, and several international trials are underway.

All the aforementioned aspects, and still others, make advisable this Topical Collection, which intends to serve as a multidisciplinary platform where urologists, oncologists, pathologists, radiologists, and basic researchers interested in clear cell renal cell carcinoma may meet and collaborate.

Dr. José I. López
Dr. Claudia Manini
Collection 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 collection 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.

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Keywords

clear cell renal cell carcinoma
pathology
diagnosis
hypoxia
intratumor heterogeneity
immune checkpoint blockage antiangiogenic therapy

Published Papers (7 papers)

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2023

Jump to: 2022

28 pages, 731 KiB

Open AccessSystematic Review

Comprehensive Systematic Review of Biomarkers in Metastatic Renal Cell Carcinoma: Predictors, Prognostics, and Therapeutic Monitoring

and

Cancers 2023, 15(20), 4934; https://doi.org/10.3390/cancers15204934 - 11 Oct 2023

Viewed by 774

Abstract

Background: Challenges remain in determining the most effective treatment strategies and identifying patients who would benefit from adjuvant or neoadjuvant therapy in renal cell carcinoma. The objective of this review is to provide a comprehensive overview of biomarkers in metastatic renal cell carcinoma (mRCC) and their utility in prediction of treatment response, prognosis, and therapeutic monitoring in patients receiving systemic therapy for metastatic disease. Methods: A systematic literature search was conducted using the PubMed database for relevant studies published between January 2017 and December 2022. The search focused on biomarkers associated with mRCC and their relationship to immune checkpoint inhibitors, targeted therapy, and VEGF inhibitors in the adjuvant, neoadjuvant, and metastatic settings. Results: The review identified various biomarkers with predictive, prognostic, and therapeutic monitoring potential in mRCC. The review also discussed the challenges associated with anti-angiogenic and immune-checkpoint monotherapy trials and highlighted the need for personalized therapy based on molecular signatures. Conclusion: This comprehensive review provides valuable insights into the landscape of biomarkers in mRCC and their potential applications in prediction of treatment response, prognosis, and therapeutic monitoring. The findings underscore the importance of incorporating biomarker assessment into clinical practice to guide treatment decisions and improve patient outcomes in mRCC. Full article

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14 pages, 557 KiB

Open AccessReview

Recent Advances in Single-Cell RNA-Sequencing of Primary and Metastatic Clear Cell Renal Cell Carcinoma

Adele M. Alchahin

Ioanna Tsea

and

Ninib Baryawno

Cancers 2023, 15(19), 4734; https://doi.org/10.3390/cancers15194734 - 26 Sep 2023

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Abstract

Over the past two decades, significant progress has been made in the treatment of clear cell renal cell carcinoma (ccRCC), with a shift towards adopting new treatment approaches ranging from monotherapy to triple-combination therapy. This progress has been spearheaded by fundamental technological advancements that have allowed a deeper understanding of the various biological components of this cancer. In particular, the rapid commercialization of transcriptomics technologies, such as single-cell RNA-sequencing (scRNA-seq) methodologies, has played a crucial role in accelerating this understanding. Through precise measurements facilitated by these technologies, the research community has successfully identified and characterized diverse tumor, immune, and stromal cell populations, uncovering their interactions and pathways involved in disease progression. In localized ccRCC, patients have shown impressive response rates to treatment. However, despite the emerging findings and new knowledge provided in the field, there are still patients that do not respond to treatment, especially in advanced disease stages. One of the key challenges lies in the limited study of ccRCC metastases compared to localized cases. This knowledge gap may contribute to the relatively low survival rates and response rates observed in patients with metastatic ccRCC. To bridge this gap, we here delve into recent research utilizing scRNA-seq technologies in both primary and metastatic ccRCC. The goal of this review is to shed light on the current state of knowledge in the field, present existing treatment options, and emphasize the crucial steps needed to improve survival rates, particularly in cases of metastatic ccRCC. Full article

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10 pages, 4087 KiB

Open AccessReview

Cystic Clear Cell Renal Cell Carcinoma: A Morphological and Molecular Reappraisal

Giacomo Maria Pini

Roberta Lucianò

and

Maurizio Colecchia

Cancers 2023, 15(13), 3352; https://doi.org/10.3390/cancers15133352 - 26 Jun 2023

Viewed by 921

Abstract

A wide variety of renal neoplasms can have cystic areas. These can occur for different reasons: some tumors have an intrinsic cystic architecture, while others exhibit pseudocystic degeneration of necrotic foci or they have cystically dilated renal tubules constrained by stromal neoplastic cells. Clear cell renal cell carcinoma (CCRCC), either solid or cystic, is the most frequent type of renal cancer. While pseudocysts are found in high-grade aggressive CCRCC, cystic growth is associated with low-grade indolent cases. The latter also form through a cyst-dependent molecular pathway, and they are more frequent in patients suffering from VHL disease. The differential diagnosis of multilocular cystic renal neoplasm of low malignant potential and clear cell papillary renal cell tumor can be especially hard and requires a focused macroscopical and microscopical pathological analysis. As every class of renal tumor includes cystic forms, knowledge of the criteria required for a differential diagnosis is mandatory. Full article

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20 pages, 1702 KiB

Open AccessReview

Understanding the Tumor Immune Microenvironment in Renal Cell Carcinoma

and

Cancers 2023, 15(9), 2500; https://doi.org/10.3390/cancers15092500 - 27 Apr 2023

Viewed by 1500

Abstract

Scientific understanding of how the immune microenvironment interacts with renal cell carcinoma (RCC) has substantially increased over the last decade as a result of research investigations and applying immunotherapies, which modulate how the immune system targets and eliminates RCC tumor cells. Clinically, immune checkpoint inhibitor therapy (ICI) has revolutionized the treatment of advanced clear cell RCC because of improved outcomes compared to targeted molecular therapies. From an immunologic perspective, RCC is particularly interesting because tumors are known to be highly inflamed, but the mechanisms underlying the inflammation of the tumor immune microenvironment are atypical and not well described. While technological advances in gene sequencing and cellular imaging have enabled precise characterization of RCC immune cell phenotypes, multiple theories have been suggested regarding the functional significance of immune infiltration in RCC progression. The purpose of this review is to describe the general concepts of the anti-tumor immune response and to provide a detailed summary of the current understanding of the immune response to RCC tumor development and progression. This article describes immune cell phenotypes that have been reported in the RCC microenvironment and discusses the application of RCC immunophenotyping to predict response to ICI therapy and patient survival. Full article

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10 pages, 520 KiB

Open AccessCommentary

Role of Clock Genes and Circadian Rhythm in Renal Cell Carcinoma: Recent Evidence and Therapeutic Consequences

Matteo Santoni

Javier Molina-Cerrillo

and

Cancers 2023, 15(2), 408; https://doi.org/10.3390/cancers15020408 - 07 Jan 2023

Cited by 1 | Viewed by 1820

Abstract

Circadian rhythm regulates cellular differentiation and physiology and shapes the immune response. Altered expression of clock genes might lead to the onset of common malignant cancers, including Renal Cell Carcinoma (RCC). Data from Cancer Genome Atlas (TCGA) indicate that clock genes PER1-3, CRY2, CLOCK, NR1D2 and RORα are overexpressed in RCC tissues and correlate with patients’ prognosis. The expression of clock genes could finely tune transcription factor activity in RCC and is associated with the extent of immune cell infiltration. The clock system interacts with hypoxia-induced factor-1α (HIF-1α) and regulates the circadian oscillation of mammalian target of rapamycin (mTOR) activity thereby conditioning the antitumor effect of mTOR inhibitors. The stimulation of natural killer (NK) cell activity exerted by the administration of interferon-α, a cornerstone of the first era of immunotherapy for RCC, relevantly varies according to circadian dosing time. Recent evidence demonstrated that time-of-day infusion directly affects the efficacy of immune checkpoint inhibitors in cancer patients. Compounds targeting the circadian clock have been identified and their role in the era of immunotherapy deserves to be further investigated. In this review, we aimed at addressing the impact of clock genes on the natural history of kidney cancer and their potential therapeutic implications. Full article

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15 pages, 321 KiB

Open AccessReview

Advances in Imaging-Based Biomarkers in Renal Cell Carcinoma: A Critical Analysis of the Current Literature

and

Cancers 2023, 15(2), 354; https://doi.org/10.3390/cancers15020354 - 05 Jan 2023

Cited by 5 | Viewed by 1829

Abstract

Cross-sectional imaging is the standard diagnostic tool to determine underlying biology in renal masses, which is crucial for subsequent treatment. Currently, standard CT imaging is limited in its ability to differentiate benign from malignant disease. Therefore, various modalities have been investigated to identify imaging-based parameters to improve the noninvasive diagnosis of renal masses and renal cell carcinoma (RCC) subtypes. MRI was reported to predict grading of RCC and to identify RCC subtypes, and has been shown in a small cohort to predict the response to targeted therapy. Dynamic imaging is promising for the staging and diagnosis of RCC. PET/CT radiotracers, such as ¹⁸F-fluorodeoxyglucose (FDG), ¹²⁴I-cG250, radiolabeled prostate-specific membrane antigen (PSMA), and ¹¹C-acetate, have been reported to improve the identification of histology, grading, detection of metastasis, and assessment of response to systemic therapy, and to predict oncological outcomes. Moreover, ⁹⁹Tc-sestamibi and SPECT scans have shown promising results in distinguishing low-grade RCC from benign lesions. Radiomics has been used to further characterize renal masses based on semantic and textural analyses. In preliminary studies, integrated machine learning algorithms using radiomics proved to be more accurate in distinguishing benign from malignant renal masses compared to radiologists’ interpretations. Radiomics and radiogenomics are used to complement risk classification models to predict oncological outcomes. Imaging-based biomarkers hold strong potential in RCC, but require standardization and external validation before integration into clinical routines. Full article

2022

Jump to: 2023

15 pages, 4019 KiB

Open AccessArticle

The Association of Tumor Immune Microenvironment of the Primary Lesion with Time to Metastasis in Patients with Renal Cell Carcinoma: A Retrospective Analysis

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Cancers 2022, 14(21), 5258; https://doi.org/10.3390/cancers14215258 - 26 Oct 2022

Viewed by 1192

Abstract

Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis. Full article

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Topical Collection "Clear Cell Renal Cell Carcinoma 2022–2023"

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Published Papers (7 papers)

2023

Jump to: 2022

2022

Jump to: 2023

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