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Cancers
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New Perspectives of Renal Cell Cancer
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New Perspectives of Renal Cell Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (10 March 2023) | Viewed by 11199

Special Issue Editor

Dr. Christopher J. Ricketts

E-Mail Website
Guest Editor
Urologic Oncology Branch (UOB), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA
Interests: cancer susceptibility syndromes; renal cell carcinoma; cancer genetics; DNA methylation

Special Issue Information

Dear Colleagues,

Renal cell carcinoma (RCC) affects over 400,000 individuals worldwide annually and is responsible for over 150,000 deaths each year. Our understanding of RCC has evolved over the past 40 years, from considering RCC as a single entity to our current understanding that RCC is made up of many different subtypes. Each subtype of renal cancer can present with distinct histologic, genetic, and molecular alterations and require different clinical management and treatment. Our ability to recognize and differentiate the multiple subtypes of RCC, in combination with our increased understanding of the biology of each subtype, has allowed for tailored surgical management and targeted precision therapies to be developed for advanced disease, such as VEGF inhibitors and checkpoint inhibitors. While these are having significant impacts in some subtypes, most only prolong survival in advanced cases and some subtypes still have no specific therapy. By uniting and furthering our knowledge in this field, we hope to improve outcomes across all patients with this wide array of RCC disease.

In this Special Issue, we aim to present a series of review articles that will highlight the progress that has been made in the diagnosis, diverse biology, and treatment of RCCs, along with the many challenges that still remain. Topics of interest include: The advancements in molecular pathology to identify the fundamentally different forms of RCC. The recent development of specific HIF2α inhibitors to target the pseudohypoxia response characteristic of ccRCC. How the study of hereditary RCC susceptibility genes continues to improve our understanding and treatment of both inherited and sporadic RCC. How intratumoral heterogeneity in ccRCC radically altered our view of the disease but provided unique insight into tumor development and evolution. How the recent proteogenomic analysis of ccRCC is opening new avenues of research. How tumor metabolism has adapted within different RCC subtypes and how this could provide tumor-specific therapeutic targets. Finally, the current state of precision medicine in the treatment of RCC and the challenges that remain to be faced and overcome.

Dr. Christopher J. Ricketts
Guest Editor

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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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.

Published Papers (7 papers)

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Research

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12 pages, 996 KiB  
Article
Oncological and Peri-Operative Outcomes of Percutaneous Cryoablation of Renal Cell Carcinoma for Patients with Hereditary RCC Diseases—An Analysis of European Multi-Centre Prospective EuRECA Registry
by Filzah Hanis Osman, Vinson Wai-Shun Chan, David J. Breen, Alexander King, Tommy Kjærgaard Nielsen, Julien Garnon, Des Alcorn, Brunolf Lagerveld, Ole Graumann, Francis Xavier Keeley, Jr., Miles Walkden, Éric de Kerviler and Tze Min Wah
Cancers 2023, 15(13), 3322; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15133322 - 24 Jun 2023
Viewed by 892
Abstract
This study aims to evaluate the safety, efficacy, and renal function preservation of percutaneous cryoablation (PCA) for small renal masses (SRMs) in inherited RCC syndromes. Patients with inherited T1N0M0 RCCs (<7 cm) undergoing PCA from 2015 to 2021 were identified from the European [...] Read more.
This study aims to evaluate the safety, efficacy, and renal function preservation of percutaneous cryoablation (PCA) for small renal masses (SRMs) in inherited RCC syndromes. Patients with inherited T1N0M0 RCCs (<7 cm) undergoing PCA from 2015 to 2021 were identified from the European Registry for Renal Cryoablation (EuRECA). The primary outcome was local recurrence-free survival (LRFS). The secondary outcomes included technical success, peri-operative outcomes, and other oncological outcomes estimated using the Kaplan–Meier method. Simple proportions, chi-squared tests, and t-tests were used to analyse the peri-operative outcomes. A total of 68 sessions of PCA were performed in 53 patients with RCC and 85 tumours were followed-up for a mean duration of 30.4 months (SD ± 22.0). The overall technical success rate was 99%. The major post-operative complication rate was 1.7%. In total, 7.4% (2/27) of patients had >25% reduction in renal function. All oncological events were observed in VHL patients. Estimated 5-year LRFS, metastasis-free survival, cancer-specific survival, and overall survival were 96.0% (95% CI 75–99%), 96.4% (95% CI 77–99%), 90.9% (95% CI 51–99%), and 90.9% (95% CI 51–99%), respectively. PCA of RCCs for patients with hereditary RCC SRMs appears to be safe, offers low complication rates, preserves renal function, and achieves good oncological outcomes. Full article
(This article belongs to the Special Issue New Perspectives of Renal Cell Cancer)
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15 pages, 2087 KiB  
Article
Efficacy and Safety of First-Line Cytokines versus Sunitinib and Second-Line Axitinib for Patients with Metastatic Renal Cell Carcinoma (ESCAPE Study): A Phase III, Randomized, Sequential Open-Label Study
by Yoshifumi Kadono, Hiroyuki Konaka, Takahiro Nohara, Kouji Izumi, Satoshi Anai, Kiyohide Fujimoto, Tomoyuki Koguchi, Kei Ishibashi, Noriyasu Kawai, Keita Nakane, Akinori Iba, Naoya Masumori, Shizuko Takahara and Atsushi Mizokami
Cancers 2023, 15(10), 2745; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15102745 - 13 May 2023
Viewed by 1264
Abstract
Background: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. Methods: This was a phase III [...] Read more.
Background: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. Methods: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. Results: Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7–46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3–26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121–1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418–6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. Conclusions: There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522. Full article
(This article belongs to the Special Issue New Perspectives of Renal Cell Cancer)
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10 pages, 320 KiB  
Article
Does the Immunohistochemical Expression of CD44, MMP-2, and MMP-9 in Association with the Histopathological Subtype of Renal Cell Carcinoma Affect the Survival of Patients with Renal Cancer?
by Magdalena Chrabańska, Magdalena Rynkiewicz, Paweł Kiczmer and Bogna Drozdzowska
Cancers 2023, 15(4), 1202; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15041202 - 14 Feb 2023
Cited by 3 | Viewed by 1203
Abstract
CD44, MMP-2, and MMP-9 are new potential molecular prognostic markers in renal cell carcinoma (RCC). The aim of the study was to analyze whether the expression of CD44, MMP-2, and MMP-9 in association with the histopathological subtype of RCC affects the survival of [...] Read more.
CD44, MMP-2, and MMP-9 are new potential molecular prognostic markers in renal cell carcinoma (RCC). The aim of the study was to analyze whether the expression of CD44, MMP-2, and MMP-9 in association with the histopathological subtype of RCC affects the survival of patients with renal cancer. The study population included 243 clear cell RCC (ccRCC) and 59 non-ccRCC cases. A total of 302 tumors were examined for CD44, MMP2, and MMP9 expression by immunohistochemistry. The expression levels of the proteins were scored by semi-quantitative methods, and the correlation with overall patient survival was verified. We found no significant differences in CD44 expression levels between cc-RCC and non-ccRCC cases; however, significant differences existed in the degree of MMP-2 and MMP-9 expression between cc-RCC and non-ccRCC cases. There was significantly higher MMP expression in non-ccRCC than in ccRCC cases. Univariate Cox regression analysis showed that increased CD44 expression and histopathological subtype of ccRCC were predictors of shorter overall survival. Moreover, MMP-2 overexpression slightly reduced the risk of patient death, while MMP-9 expression did not show an association with patients’ survival. However, on multivariate analysis, only the histopathological subtypes of ccRCC and CD44 expression were independent risk factors for patient death. Full article
(This article belongs to the Special Issue New Perspectives of Renal Cell Cancer)
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Review

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17 pages, 3594 KiB  
Review
Recent Advances in Renal Tumors with TSC/mTOR Pathway Abnormalities in Patients with Tuberous Sclerosis Complex and in the Sporadic Setting
by Payal Kapur, James Brugarolas and Kiril Trpkov
Cancers 2023, 15(16), 4043; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15164043 - 10 Aug 2023
Cited by 4 | Viewed by 1608
Abstract
A spectrum of renal tumors associated with frequent TSC/mTOR (tuberous sclerosis complex/mechanistic target of rapamycin) pathway gene alterations (in both the germline and sporadic settings) have recently been described. These include renal cell carcinoma with fibromyomatous stroma (RCC FMS), eosinophilic solid and cystic [...] Read more.
A spectrum of renal tumors associated with frequent TSC/mTOR (tuberous sclerosis complex/mechanistic target of rapamycin) pathway gene alterations (in both the germline and sporadic settings) have recently been described. These include renal cell carcinoma with fibromyomatous stroma (RCC FMS), eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumor (EVT), and low-grade oncocytic tumor (LOT). Most of these entities have characteristic morphologic and immunohistochemical features that enable their recognition without the need for molecular studies. In this report, we summarize recent advances and discuss their evolving complexity. Full article
(This article belongs to the Special Issue New Perspectives of Renal Cell Cancer)
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13 pages, 692 KiB  
Review
The Judicious Use of Stereotactic Ablative Radiotherapy in the Primary Management of Localized Renal Cell Carcinoma
by Andrew B. Barbour, Simon Kirste, Anca-Liga Grosu, Shankar Siva, Alexander V. Louie, Hiroshi Onishi, Anand Swaminath, Bin S. Teh, Sarah P. Psutka, Emily S. Weg, Jonathan J. Chen, Jing Zeng, John L. Gore, Evan Hall, Jay J. Liao, Rohann J. M. Correa and Simon S. Lo
Cancers 2023, 15(14), 3672; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15143672 - 19 Jul 2023
Viewed by 1590
Abstract
Localized renal cell carcinoma is primarily managed surgically, but this disease commonly presents in highly comorbid patients who are poor operative candidates. Less invasive techniques, such as cryoablation and radiofrequency ablation, are effective, but require percutaneous or laparoscopic access, while generally being limited [...] Read more.
Localized renal cell carcinoma is primarily managed surgically, but this disease commonly presents in highly comorbid patients who are poor operative candidates. Less invasive techniques, such as cryoablation and radiofrequency ablation, are effective, but require percutaneous or laparoscopic access, while generally being limited to cT1a tumors without proximity to the renal pelvis or ureter. Active surveillance is another management option for small renal masses, but many patients desire treatment or are poor candidates for active surveillance. For poor surgical candidates, a growing body of evidence supports stereotactic ablative radiotherapy (SABR) as a safe and effective non-invasive treatment modality. For example, a recent multi-institution individual patient data meta-analysis of 190 patients managed with SABR estimated a 5.5% five-year cumulative incidence of local failure with one patient experiencing grade 4 toxicity, and no other grade ≥3 toxic events. Here, we discuss the recent developments in SABR for the management of localized renal cell carcinoma, highlighting key concepts of appropriate patient selection, treatment design, treatment delivery, and response assessment. Full article
(This article belongs to the Special Issue New Perspectives of Renal Cell Cancer)
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20 pages, 6240 KiB  
Review
MRI Characteristics of Pediatric and Young-Adult Renal Cell Carcinoma: A Single-Center Retrospective Study and Literature Review
by Justine N. van der Beek, Ronald R. de Krijger, Rutger A. J. Nievelstein, Axel Bex, Aart J. Klijn, Marry M. van den Heuvel-Eibrink and Annemieke S. Littooij
Cancers 2023, 15(5), 1401; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051401 - 22 Feb 2023
Cited by 1 | Viewed by 1568
Abstract
Pediatric renal cell carcinoma (RCC) is a rare malignancy. Magnetic resonance imaging (MRI) is the preferred imaging modality for assessment of these tumors. The previous literature has suggested that cross-sectional-imaging findings differ between RCC and other pediatric renal tumors and between RCC subtypes. [...] Read more.
Pediatric renal cell carcinoma (RCC) is a rare malignancy. Magnetic resonance imaging (MRI) is the preferred imaging modality for assessment of these tumors. The previous literature has suggested that cross-sectional-imaging findings differ between RCC and other pediatric renal tumors and between RCC subtypes. However, studies focusing on MRI characteristics are limited. Therefore, this study aims to identify MRI characteristics of pediatric and young-adult RCC, through a single-center case series and literature review. Six identified diagnostic MRI scans were retrospectively assessed, and an extensive literature review was conducted. The included patients had a median age of 12 years (63–193 months). Among other subtypes, 2/6 (33%) were translocation-type RCC (MiT-RCC) and 2/6 (33%) were clear-cell RCC. Median tumor volume was 393 cm3 (29–2191 cm3). Five tumors had a hypo-intense appearance on T2-weighted imaging, whereas 4/6 were iso-intense on T1-weighted imaging. Four/six tumors showed well-defined margins. The median apparent diffusion coefficient (ADC) values ranged from 0.70 to 1.20 × 10−3 mm2/s. In thirteen identified articles focusing on MRI characteristics of MiT-RCC, the majority of the patients also showed T2-weighted hypo-intensity. T1-weighted hyper-intensity, irregular growth pattern and limited diffusion–restriction were also often described. Discrimination of RCC subtypes and differentiation from other pediatric renal tumors based on MRI remains difficult. Nevertheless, T2-weighted hypo-intensity of the tumor seems a potential distinctive characteristic. Full article
(This article belongs to the Special Issue New Perspectives of Renal Cell Cancer)
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9 pages, 503 KiB  
Review
New Paradigms for Cytoreductive Nephrectomy
by Benjamin J. Lichtbroun, Arnav Srivastava, Sai Krishnaraya Doppalapudi, Kevin Chua and Eric A. Singer
Cancers 2022, 14(11), 2660; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112660 - 27 May 2022
Cited by 6 | Viewed by 2058
Abstract
The role of CN in the treatment of metastatic renal cell carcinoma (mRCC) has been studied over the course of the past few decades. With the advent of immuno-oncologic (IO) agents, there has been a paradigm shift in the treatment of RCC. Within [...] Read more.
The role of CN in the treatment of metastatic renal cell carcinoma (mRCC) has been studied over the course of the past few decades. With the advent of immuno-oncologic (IO) agents, there has been a paradigm shift in the treatment of RCC. Within this new era of cancer care, the role of CN is unclear. There are several studies currently underway that aim to assess the role of CN in combination with these therapies. We reviewed articles examining CN, both historically and in the modern immunotherapy era. While immune-oncologic agents are relatively new and large clinical trials have yet to be completed, data thus far is promising that CN may provide clinical benefit. Multiple ongoing trials may clarify the role of CN in this new era of cancer care. Full article
(This article belongs to the Special Issue New Perspectives of Renal Cell Cancer)
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